The DOI matches its Crossref record; 225 of the 225 references it cites were found in a registry or an index; 13 of the 239 sources its claims cite were checked for support.
Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress
Open accessAbstract
To maintain genome stability, cells have evolved various DNA repair pathways to deal with oxidative DNA damage. DNA damage response (DDR) pathways, including ATM-Chk2 and ATR-Chk1 checkpoints, are also activated in oxidative stress to coordinate DNA repair, cell cycle progression, transcription, apoptosis, and senescence. Several studies demonstrate that DDR pathways can regulate DNA repair pathways. On the other hand, accumulating evidence suggests that DNA repair pathways may modulate DDR pathway activation as well. In this review, we summarize our current understanding of how various DNA repair and DDR pathways are activated in response to oxidative DNA damage primarily from studies in eukaryotes. In particular, we analyze the functional interplay between DNA repair and DDR pathways in oxidative stress. A better understanding of cellular response to oxidative stress may provide novel avenues of treating human diseases, such as cancer and neurodegenerative disorders.
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Written from the paper’s full text.
TL;DR
This review summarizes how oxidative stress activates ATM-Chk2 and ATR-Chk1 DNA damage response (DDR) pathways and how these pathways functionally interact with DNA repair pathways such as BER/SSBR, NER, MMR, HR, and NHEJ. It argues that DDR and DNA repair are integrated networks in oxidative stress, with unresolved questions about crosstalk and disease relevance.
Key findings
- Oxidative stress is estimated to induce approximately 10,000 DNA alterations per cell per day, and can generate base damage, AP sites, SSBs, DSBs, crosslinks, stalled replication forks, and oxidatively-generated clustered DNA lesions.
- ATM-Chk2 is activated primarily by DSBs, but oxidative stress can also activate ATM, as shown by hydrogen peroxide-induced ATM autophosphorylation at Serine 1981, p53 phosphorylation at Serine 15, and Chk2 phosphorylation at Threonine 68, even without H2AX phosphorylation at Serine 139.
- ATR-Chk1 is activated by replication stress and other damage; hyperoxia (95% oxygen versus normal 21% oxygen) induced ATR-dependent but ATM-independent Chk1 phosphorylation at Serine 345 and p53 phosphorylation in A549 cells.
- DDR pathways regulate DNA repair, and DNA repair proteins also regulate DDR: for example, Chk2-dependent XRCC1 phosphorylation at Threonine 284 promotes XRCC1 recruitment, ATM-dependent TDP1 phosphorylation at Serine 81 facilitates TDP1 recruitment, and APE2 is required for ATR-Chk1 checkpoint activation in oxidative stress.
Methods
- Design: narrative review of current understanding of oxidative stress-induced DNA damage, DDR pathways, and DNA repair pathways, primarily from studies in eukaryotes.
- Data or sample: no primary experimental sample; the paper synthesizes published literature and cites studies in human cell lines, Xenopus egg extracts, yeast, and other model systems.
- Main analysis: conceptual synthesis of ATM-Chk2 and ATR-Chk1 activation mechanisms, crosstalk between them, and functional connections with BER/SSBR, NER, MMR, HR, and NHEJ, supported by schematic figures.
Limitations
- Stated in the paper: it remains challenging to quantitatively measure oxidatively-generated DNA damage without measuring intermediate repair products; it is elusive how accumulation of unrepaired oxidative DNA damage leads to cancer and neurodegenerative diseases; more investigation is needed on interplay between ATM/ATR-mediated DDR and DNA damage tolerance pathways; and it is unclear how ATM-Chk2 and ATR-Chk1 crosstalk in oxidative stress.
- Evident from the text: this is a narrative review rather than a systematic review or meta-analysis, and it focuses on higher eukaryotic model organisms.
- Evident from the text: many mechanistic details remain unresolved, including exactly how DDR pathways regulate DNA repair in oxidative stress, whether ATR or Chk1 kinase activity directly regulates BER, and how the 9-1-1 complex stimulates BER at nearly all steps.
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Claims the paper makes
134 Not checked yet · 13 Own interpretation · 3 Partly supported · 3 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The PCNA-like clamp 9-1-1 complex (Rad9-Rad1-Hus1) is recruited preferentially to the 5′-primed ssDNA/dsDNA junction by RPA and the clamp loader Rad17-RFC complex [102–105].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATR-Chk1 checkpoint activation in oxidative stress
What the sources say
- Supportedcites [102] Ellison V, Stillman B (2003) Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5′ recessed DNA. PLoS Biol 1(2):E33. doi: 10.1371/journal.pbio.0000033 source
The Results section on DNA substrate specificity reports that Rad17–RFC (RSR) loads the Rad9–Hus1–Rad1 clamp much more effectively onto a 5′-recessed primer–template junction than onto a 3′-recessed one. The same section reports that loading requires RPA. The paper demonstrates this in vitro; the citing sentence does not explicitly claim an in-vivo result. (LLM, conf=0.93)
- Not checked yetcites [103] Parrilla-Castellar ER, Arlander SJ, Karnitz L (2004) Dial 9-1-1 for DNA damage: the Rad9-Hus1-Rad1 (9-1-1) clamp complex. DNA Repair 3(8–9):1009–1014. doi: 10.1016/j.dnarep.2004.03.032 source
- Partly supportedcites [104] Bermudez VP, Lindsey-Boltz LA, Cesare AJ, Maniwa Y, Griffith JD, Hurwitz J, Sancar A (2003) Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro. Proc Natl Acad Sci USA 100(4):1633–1638. doi: 10.1073/pnas.0437927100 sourceExperimental — accuracy not yet measured
The Results (page unavailable) show that Rad17-RFC recruits the 9-1-1 complex to nicked or gapped DNA, and the Abstract identifies 9-1-1 as a PCNA-like Rad9–Rad1–Hus1 complex. Our copy does not establish that RPA mediates recruitment or that recruitment is preferential to a 5′-primed ssDNA/dsDNA junction. (LLM, conf=0.88)
- Not checked yetcites [105] Majka J, Binz SK, Wold MS, Burgers PM (2006) Replication protein A directs loading of the DNA damage checkpoint clamp to 5′-DNA junctions. J Biol Chem 281(38):27855–27861. doi: 10.1074/jbc.M605176200 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“As a critical component of ATR-Chk1 checkpoint pathway, the 9-1-1 complex interacts with several BER proteins: APE1, Polymerase β (Pol β), FEN1, DNA ligase I, as well as DNA glycosylases MutY, NEIL1, and TDG, thereby stimulating their DNA repair activities [177–185] (Fig. 3).”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
What the sources say
- Supportedcites [177] Toueille M, El-Andaloussi N, Frouin I, Freire R, Funk D, Shevelev I, Friedrich-Heineken E, Villani G, Hottiger MO, Hubscher U (2004) The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase beta and increases its DNA substrate utilisation efficiency: implications for DNA repair. Nucleic Acids Res 32(11):3316–3324. doi: 10.1093/nar/gkh652 source
Among the several proteins and citations in the sentence, this paper supports the Pol β component. The Introduction and Discussion report a direct interaction between 9-1-1 and Pol β and stimulation of Pol β DNA synthesis on a substrate mimicking a BER intermediate. (LLM, conf=0.88)
- Supportedcites [178] Wang W, Brandt P, Rossi ML, Lindsey-Boltz L, Podust V, Fanning E, Sancar A, Bambara RA (2004) The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1. Proc Natl Acad Sci USA 101(48):16762–16767. doi: 10.1073/pnas.0407686101 source
This source supports the FEN1 portion of the multi-citation sentence. The Discussion states that 9-1-1 interacts with FEN1 and stimulates its cleavage activity; the Results report stimulation on several substrates. (LLM, conf=0.92)
- Partly supportedcites [179] Chang DY, Lu AL (2005) Interaction of checkpoint proteins Hus1/Rad1/Rad9 with DNA base excision repair enzyme MutY homolog in fission yeast, Schizosaccharomyces pombe. J Biol Chem 280(1):408–417. doi: 10.1074/jbc.M406800200 sourceExperimental — accuracy not yet measured
The Discussion (page not available in our copy) reports that fission-yeast MutY homolog SpMYH interacts with each subunit of the 9-1-1 complex. This supports the MutY interaction attributed to this source, but the paper describes the interaction as part of a DNA-damage signaling model; it does not report that 9-1-1 stimulates MYH’s DNA repair activity. The other listed BER proteins are not the part of the multi-citation sentence assessed against this source. (LLM, conf=0.88)
- Not checked yetcites [180] Friedrich-Heineken E, Toueille M, Tannler B, Burki C, Ferrari E, Hottiger MO, Hubscher U (2005) The two DNA clamps Rad9/Rad1/Hus1 complex and proliferating cell nuclear antigen differentially regulate flap endonuclease 1 activity. J Mol Biol 353(5):980–989. doi: 10.1016/j.jmb.2005.09.018 source
- Supportedcites [181] Smirnova E, Toueille M, Markkanen E, Hubscher U (2005) The human checkpoint sensor and alternative DNA clamp Rad9-Rad1-Hus1 modulates the activity of DNA ligase I, a component of the long-patch base excision repair machinery. Biochem J 389(Pt 1):13–17. doi: 10.1042/BJ20050211 source
For this citation within a grouped citation, the relevant claim is the interaction with DNA ligase I and stimulation of its activity. The Introduction describes a physical and functional interaction between 9-1-1 and DNA ligase I, and the Results report stimulation of ligase I activity in vitro. (LLM, conf=0.92)
- Partly supportedcites [182] Wang W, Lindsey-Boltz LA, Sancar A, Bambara RA (2006) Mechanism of stimulation of human DNA ligase I by the Rad9-rad1-Hus1 checkpoint complex. J Biol Chem 281(30):20865–20872. doi: 10.1074/jbc.M602289200 sourceExperimental — accuracy not yet measured
The Abstract and Discussion report that 9-1-1 interacts with BER proteins and stimulates Pol β, FEN1, and DNA ligase I. The Abstract also reports binding to a MutY homolog, but not stimulation of its repair activity. The passages do not identify APE1, NEIL1, or TDG as interacting partners or report stimulation of their activities. (LLM, conf=0.90)
- Partly supportedcites [183] Guan X, Bai H, Shi G, Theriot CA, Hazra TK, Mitra S, Lu AL (2007) The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates NEIL1 glycosylase. Nucleic Acids Res 35(8):2463–2472. doi: 10.1093/nar/gkm075 sourceExperimental — accuracy not yet measured
The Introduction and Discussion report that 9-1-1 interacts with and stimulates MYH (a MutY homolog), Pol β, FEN1, DNA ligase I, and NEIL1. The Discussion mentions APE1 as a BER component but does not say 9-1-1 interacts with or stimulates it; no passage found supports the claim about TDG. No page numbers were provided in our copy. (LLM, conf=0.89)
- Partly supportedcites [184] Gembka A, Toueille M, Smirnova E, Poltz R, Ferrari E, Villani G, Hubscher U (2007) The checkpoint clamp, Rad9-Rad1-Hus1 complex, preferentially stimulates the activity of apurinic/apyrimidinic endonuclease 1 and DNA polymerase beta in long patch base excision repair. Nucleic Acids Res 35(8):2596–2608. doi: 10.1093/nar/gkl1139 sourceExperimental — accuracy not yet measured
The Introduction (page not supplied) reports physical and functional interactions with Pol β, FEN1, DNA ligase I, and a MutY homolog; the paper also reports interaction with and stimulation of APE1. It does not address NEIL1 or TDG. The Discussion (page not supplied) adds that, in this paper’s reconstituted repair assay, 9-1-1 did not stimulate FEN1 or DNA ligase I, although earlier studies had reported stimulation. (LLM, conf=0.87)
- Supportedcites [185] Guan X, Madabushi A, Chang DY, Fitzgerald ME, Shi G, Drohat AC, Lu AL (2007) The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates DNA repair enzyme TDG glycosylase. Nucleic Acids Res 35(18):6207–6218. doi: 10.1093/nar/gkm678 source
The Introduction identifies MYH (a MutY homolog), NEIL1, APE1, Pol β, FEN1, and DNA ligase I as proteins that interact with the 9-1-1 complex, and describes stimulation of the other BER enzymes. The Discussion states that the complex interacts with and stimulates those enzymes and reports this study’s finding that it also interacts with and stimulates TDG. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
None of the sources cited for this claim have been checked yet.
In the paper
“Under normal conditions, ATM is inactive in a dimer or higher-order oligomer status, when its kinase domain is bound by a region surrounding a critical Serine 1981 and prevented from activation.”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [50] Bakkenist CJ, Kastan MB (2004) Initiating cellular stress responses. Cell 118(1):9–17. doi: 10.1016/j.cell.2004.06.023 source
- Not checked yetcites [51] Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421(6922):499–506. doi: 10.1038/nature01368 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“An in vitro reconstitution analysis further revealed that the MRN complex stimulates ATM kinase activity toward its substrates such as Chk2, p53, and histone H2AX [57]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [57] Lee JH, Paull TT (2004) Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304(5667):93–96. doi: 10.1126/science.1091496 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In an ischemic retinopathy model, ATM activation by ROS promotes endothelial proliferation by suppressing ROS accumulation as a feedback mechanism [68].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [68] Okuno Y, Nakamura-Ishizu A, Otsu K, Suda T, Kubota Y (2012) Pathological neoangiogenesis depends on oxidative stress regulation by ATM. Nat Med 18(8):1208–1216. doi: 10.1038/nm.2846 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“However, in response to DSBs, ATM auto-phosphorylates Serine 1981, leading to dimer dissociation into a monomer and the full activation of ATM [50, 51].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [50] Bakkenist CJ, Kastan MB (2004) Initiating cellular stress responses. Cell 118(1):9–17. doi: 10.1016/j.cell.2004.06.023 source
- Not checked yetcites [51] Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421(6922):499–506. doi: 10.1038/nature01368 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Oxidative stress by hypoxia-reoxygenation in endothelial cells may induce more profound damage, such as chromosomal aberrations (e.g., dicentric chromosomes) and micronuclei [26].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Oxidative stress-induced DNA damage
What the sources say
- Not checked yetcites [26] Bresgen N, Karlhuber G, Krizbai I, Bauer H, Bauer HC, Eckl PM (2003) Oxidative stress in cultured cerebral endothelial cells induces chromosomal aberrations, micronuclei, and apoptosis. J Neurosci Res 72(3):327–333. doi: 10.1002/jnr.10582 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ATM appears to be activated in oxidative stress response.”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In response to oxidative DNA damage, various DNA repair and DNA damage response (DDR) pathways are employed by cells to maintain genomic integrity [12, 18, 19, 31]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress
What the sources say
- Not checked yetcites [12] Barzilai A, Yamamoto K (2004) DNA damage responses to oxidative stress. DNA Repair (Amst) 3(8–9):1109–1115. doi: 10.1016/j.dnarep.2004.03.002 source
- Not checked yetcites [18] Friedberg EC (2003) DNA damage and repair. Nature 421(6921):436–440. doi: 10.1038/nature01408 source
- Not checked yetcites [19] Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179–204. doi: 10.1016/j.molcel.2010.09.019 source
- Not checked yetcites [31] Chen BP, Li M, Asaithamby A (2012) New insights into the roles of ATM and DNA-PKcs in the cellular response to oxidative stress. Cancer Lett 327(1–2):103–110. doi: 10.1016/j.canlet.2011.12.004 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Ataxia-telangiectasia mutated (ATM)-Checkpoint kinase 2 (Chk2) and ATM- and Rad3-related (ATR)-Checkpoint kinase 1 (Chk1) checkpoints are the two major DDR pathways induced by oxidatively damaged DNA to coordinate DNA repair process and cell cycle progression (Figs. 2, 7) [31, 32].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress
What the sources say
- Not checked yetcites [31] Chen BP, Li M, Asaithamby A (2012) New insights into the roles of ATM and DNA-PKcs in the cellular response to oxidative stress. Cancer Lett 327(1–2):103–110. doi: 10.1016/j.canlet.2011.12.004 source
- Not checked yetcites [32] Cimprich KA, Cortez D (2008) ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9(8):616–627. doi: 10.1038/nrm2450 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 63
- Probably not a substantial claim. 11
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Notably, ATM was directly activated by hydrogen peroxide-induced oxidation in the absence of DNA damage, evidenced by ATM auto-phosphorylation at Serine 1981, p53 phosphorylation at Serine 15, and Chk2 phosphorylation at Threonine 68, but not by H2AX phosphorylation at Serine139 [74–76].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Partly supportedcites [74] Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT (2010) ATM activation by oxidative stress. Science 330(6003):517–521. doi: 10.1126/science.1192912 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [75] Ambrose M, Gatti RA (2013) Pathogenesis of ataxia-telangiectasia: the next generation of ATM functions. Blood 121(20):4036–4045. doi: 10.1182/blood-2012-09-456897 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [76] Bhatti S, Kozlov S, Farooqi AA, Naqi A, Lavin M, Khanna KK (2011) ATM protein kinase: the linchpin of cellular defenses to stress. Cell Mol Life Sci 68(18):2977–3006. doi: 10.1007/s00018-011-0683-9 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
None of the sources cited for this claim have been checked yet.
In the paper
“Oxidative stress can induce a variety of different types of DNA damage or replication stress, such as base (purine and pyrimidine) damage, sugar moiety damage, Apurinic/apyrimidinic (AP) sites, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), tandem base modifications (e.g., DNA intrastrand crosslink), DNA interstrand crosslinks, protein–DNA crosslinks, mismatched pairs with dam”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Oxidative stress-induced DNA damage
What the sources say
- Not checked yetcites [17] Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 362:709–715 source
- Not checked yetcites [18] Friedberg EC (2003) DNA damage and repair. Nature 421(6921):436–440. doi: 10.1038/nature01408 source
- Not checked yetcites [19] Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179–204. doi: 10.1016/j.molcel.2010.09.019 source
- Not checked yetcites [20] Hoeijmakers JH (2009) DNA damage, aging, and cancer. N Engl J Med 361(15):1475–1485. doi: 10.1056/NEJMra0804615 source
- Not checked yetcites [21] Cadet J, Ravanat JL, TavernaPorro M, Menoni H, Angelov D (2012) Oxidatively generated complex DNA damage: tandem and clustered lesions. Cancer Lett 327(1–2):5–15. doi: 10.1016/j.canlet.2012.04.005 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It is estimated that oxidative stress may induce approximately 10,000 DNA alterations per cell per day, representing a major portion of endogenous DNA damage [17–20].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Oxidative stress-induced DNA damage
What the sources say
- Not checked yetcites [17] Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 362:709–715 source
- Not checked yetcites [18] Friedberg EC (2003) DNA damage and repair. Nature 421(6921):436–440. doi: 10.1038/nature01408 source
- Not checked yetcites [19] Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179–204. doi: 10.1016/j.molcel.2010.09.019 source
- Not checked yetcites [20] Hoeijmakers JH (2009) DNA damage, aging, and cancer. N Engl J Med 361(15):1475–1485. doi: 10.1056/NEJMra0804615 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Hydrogen peroxide treatment in primary neuron cells triggers γ-H2AX, indicating DSB generation and ATM activation [69].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [69] Singh S, Englander EW (2012) Nuclear depletion of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is an indicator of energy disruption in neurons. Free Radic Biol Med 53(9):1782–1790. doi: 10.1016/j.freeradbiomed.2012.07.025 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“As an ATM substrate, histone H2AX is phosphorylated at Serine 139, which is referred to γ-H2AX and prevents DSBs from processing into chromosomal translocations [58, 59].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [58] Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273(10):5858–5868 source
- Not checked yetcites [59] Franco S, Gostissa M, Zha S, Lombard DB, Murphy MM, Zarrin AA, Yan C, Tepsuporn S, Morales JC, Adams MM, Lou Z, Bassing CH, Manis JP, Chen J, Carpenter PB, Alt FW (2006) H2AX prevents DNA breaks from progressing to chromosome breaks and translocations. Mol Cell 21(2):201–214. doi: 10.1016/j.molcel.2006.01.005 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The MRN complex (Mre11-Rad50-Nbs1) is involved in ataxia-telangiectasia like disease and Nijmegen breakage syndrome and is required for ATM activation in DSB response [52–54].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [52] Uziel T, Lerenthal Y, Moyal L, Andegeko Y, Mittelman L, Shiloh Y (2003) Requirement of the MRN complex for ATM activation by DNA damage. EMBO J 22(20):5612–5621. doi: 10.1093/emboj/cdg541 source
- Not checked yetcites [53] van den Bosch M, Bree RT, Lowndes NF (2003) The MRN complex: coordinating and mediating the response to broken chromosomes. EMBO Rep 4(9):844–849. doi: 10.1038/sj.embor.embor925 source
- Not checked yetcites [54] Costanzo V, Paull T, Gottesman M, Gautier J (2004) Mre11 assembles linear DNA fragments into DNA damage signaling complexes. PLoS Biol 2(5):E110. doi: 10.1371/journal.pbio.0020110 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“ATM is a defective gene in Ataxia-telangiectasia (A-T), an autosomal recessive disorder with early onset progressive cerebellar ataxia, oculocutaneous telangiectasia, and lymphoid tumor susceptibility [48, 49].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [48] Lavin MF (2008) Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 9(10):759–769. doi: 10.1038/nrm2514 source
- Not checked yetcites [49] Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268(5218):1749–1753 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Singlet oxygen reacts with all four deoxynucleotide bases with guanine as its preference, generating 8-oxo-7,8-dihydroguanine (8-oxo-G) as the major product [5].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Oxidative stress-induced DNA damage
What the sources say
- Not checked yetcites [5] Agnez-Lima LF, Melo JT, Silva AE, Oliveira AH, Timoteo AR, Lima-Bessa KM, Martinez GR, Medeiros MH, Di Mascio P, Galhardo RS, Menck CF (2012) DNA damage by singlet oxygen and cellular protective mechanisms. Mutat Res 751(1):15–28. doi: 10.1016/j.mrrev.2011.12.005 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Hydroxyl radicals can react with the purines and pyrimidines of DNA by the addition of double bonds and the abstraction of a H atom (H·) from the methyl group of thymine and from each of the C–H bonds of 2′-deoxyribose. This results in products, such as 5-hydroxymethyl-uracil, C8–OH–adduct radical of guanine, and 8-hydroxyguanine (8-OH-G) [22].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Oxidative stress-induced DNA damage
What the sources say
- Not checked yetcites [22] Neeley WL, Essigmann JM (2006) Mechanisms of formation, genotoxicity, and mutation of guanine oxidation products. Chem Res Toxicol 19(4):491–505. doi: 10.1021/tx0600043 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Acting as a DSB sensor, the MRN complex binds to DSBs and recruits ATM to the broken DNA ends for activation.”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“To maintain genome stability, the DDR pathways are conserved surveillance mechanisms coordinating DNA repair, cell cycle progression, transcription, apoptosis, and senescence [19, 39–41].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress
What the sources say
- Not checked yetcites [19] Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179–204. doi: 10.1016/j.molcel.2010.09.019 source
- Not checked yetcites [39] Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461(7267):1071–1078. doi: 10.1038/nature08467 source
- Not checked yetcites [40] Marechal A, Zou L (2013) DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb Perspect Biol 5(9):a012716. doi: 10.1101/cshperspect.a012716 source
- Not checked yetcites [41] Branzei D, Foiani M (2010) Maintaining genome stability at the replication fork. Nat Rev Mol Cell Biol 11(3):208–219. doi: 10.1038/nrm2852 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Intrastrand crosslinks, interstrand crosslinks, DSBs, and OCDLs can be formed after exposure to IR and UV radiations [21].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Oxidative stress-induced DNA damage
What the sources say
- Not checked yetcites [21] Cadet J, Ravanat JL, TavernaPorro M, Menoni H, Angelov D (2012) Oxidatively generated complex DNA damage: tandem and clustered lesions. Cancer Lett 327(1–2):5–15. doi: 10.1016/j.canlet.2012.04.005 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“With a forkhead-associated (FHA) domain and two BRCT domains, MDC1 is phosphorylated by ATM and relocalizes to damage sites that contain the MRN complex, γ-H2AX, and 53BP1, thereby playing an indispensable role in ATM-dependent DNA damage checkpoint [61].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [61] Goldberg M, Stucki M, Falck J, D’Amours D, Rahman D, Pappin D, Bartek J, Jackson SP (2003) MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 421(6926):952–956. doi: 10.1038/nature01445 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“If not repaired, DSBs can lead to chromosomal aberrations and the dysfunction of key proteins for cell survival or viability [45–47].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [45] Karagiannis TC, El-Osta A (2004) Double-strand breaks: signaling pathways and repair mechanisms. Cell Mol Life Sci 61(17):2137–2147. doi: 10.1007/s00018-004-4174-0 source
- Not checked yetcites [46] Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 27(3):247–254. doi: 10.1038/85798 source
- Not checked yetcites [47] van Gent DC, Hoeijmakers JH, Kanaar R (2001) Chromosomal stability and the DNA double-stranded break connection. Nat Rev Genet 2(3):196–206. doi: 10.1038/35056049 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Chem-otherapeutic agents can generate oxidative DNA damage. For example, artesunate can induce 1,N6-ethenoadenine, SSBs and replication-associated DSBs [23–25].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Oxidative stress-induced DNA damage
What the sources say
- Not checked yetcites [23] Litwin I, Bocer T, Dziadkowiec D, Wysocki R (2013) Oxidative stress and replication-independent DNA breakage induced by arsenic in Saccharomyces cerevisiae. PLoS Genet 9(7):e1003640. doi: 10.1371/journal.pgen.1003640 source
- Not checked yetcites [24] Kessel M, Liu SX, Xu A, Santella R, Hei TK (2002) Arsenic induces oxidative DNA damage in mammalian cells. Mol Cell Biochem 234–235(1–2):301–308 source
- Not checked yetcites [25] Berdelle N, Nikolova T, Quiros S, Efferth T, Kaina B (2011) Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells. Mol Cancer Ther 10(12):2224–2233. doi: 10.1158/1535-7163.MCT-11-0534 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“During DNA replication, an oxidatively damaged site may be bypassed by incorporating a mismatched deoxynucleotide (e.g., 8-oxo-G:A) [7].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Oxidative stress-induced DNA damage
What the sources say
- Not checked yetcites [7] Berquist BR, Wilson DM 3rd (2012) Pathways for repairing and tolerating the spectrum of oxidative DNA lesions. Cancer Lett 327(1–2):61–72. doi: 10.1016/j.canlet.2012.02.001 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Defective DNA repair and DDR pathways may lead to several human diseases, such as cancer and neurodegenerative diseases [6, 33–38]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress
What the sources say
- Not checked yetcites [6] Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90(17):7915–7922 source
- Not checked yetcites [33] Wallace SS, Murphy DL, Sweasy JB (2012) Base excision repair and cancer. Cancer Lett 327(1–2):73–89. doi: 10.1016/j.canlet.2011.12.038 source
- Not checked yetcites [34] Raetz AG, Xie Y, Kundu S, Brinkmeyer MK, Chang C, David SS (2012) Cancer-associated variants and a common polymorphism of MUTYH exhibit reduced repair of oxidative DNA damage using a GFP-based assay in mammalian cells. Carcinogenesis 33(11):2301–2309. doi: 10.1093/carcin/bgs270 source
- Not checked yetcites [35] Xiao X, Melton DW, Gourley C (2013) Mismatch repair deficiency in ovarian cancer—molecular characteristics and clinical implications. Gynecol Oncol 132(2):506–512. doi: 10.1016/j.ygyno.2013.12.003 source
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- Not checked yetcites [37] Bouwman P, Jonkers J (2012) The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance. Nat Rev Cancer 12(9):587–598. doi: 10.1038/nrc3342 source
- Not checked yetcites [38] Hegde ML, Mantha AK, Hazra TK, Bhakat KK, Mitra S, Szczesny B (2012) Oxidative genome damage and its repair: implications in aging and neurodegenerative diseases. Mech Ageing Dev 133(4):157–168. doi: 10.1016/j.mad.2012.01.005 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“RNF4, a SUMO-targeted ubiquitin E3 ligase, is recruited to DSBs by MDC1 and promotes DNA repair and cellular response to DSBs [66, 67].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [66] Yin Y, Seifert A, Chua JS, Maure JF, Golebiowski F, Hay RT (2012) SUMO-targeted ubiquitin E3 ligase RNF4 is required for the response of human cells to DNA damage. Genes Dev 26(11):1196–1208. doi: 10.1101/gad.189274.112 source
- Not checked yetcites [67] Galanty Y, Belotserkovskaya R, Coates J, Jackson SP (2012) RNF4, a SUMO-targeted ubiquitin E3 ligase, promotes DNA double-strand break repair. Genes Dev 26(11):1179–1195. doi: 10.1101/gad.188284.112 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The phosphorylation of Chk1 enhances Chk1’s kinase activity, which in turn phosphorylates downstream substrates (e.g., Cdc25, BLM, and FANCD2/FANCE) and facilitates cell cycle arrest and DNA damage repair [91–93].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATR-Chk1 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [91] Sanchez Y (1997) Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 277(5331):1497–1501. doi: 10.1126/science.277.5331.1497 source
- Not checked yetcites [92] Boddy MN (1998) Replication checkpoint enforced by kinases Cds1 and Chk1. Science 280(5365):909–912. doi: 10.1126/science.280.5365.909 source
- Not checked yetcites [93] Zhang Y, Hunter T (2013) Roles of Chk1 in cell biology and cancer therapy. Int J Cancer 134(5):1013–1023. doi: 10.1002/ijc.28226 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Aberrant expression of ATR results in Seckel syndrome, an autosomal recessive disorder associated with growth retardation and microcephaly [82].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATR-Chk1 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [82] O’Driscoll M, Ruiz-Perez VL, Woods CG, Jeggo PA, Goodship JA (2003) A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat Genet 33(4):497–501. doi: 10.1038/ng1129 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Hydrogen peroxide induces p53 phosphorylation at Serine 15 and cell cycle arrest in an ATM-dependent manner in human umbilical vein endothelial cells [70].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [70] Chen K, Albano A, Ho A, Keaney JF Jr (2003) Activation of p53 by oxidative stress involves platelet-derived growth factor-beta receptor-mediated ataxia telangiectasia mutated (ATM) kinase activation. J Biol Chem 278(41):39527–39533. doi: 10.1074/jbc.M304423200 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The circadian protein Tim (Timeless) -Tipin (Timeless-interacting protein) complex associates with ATR-Chk1 checkpoint proteins and plays an essential role in DDR as well [130–133].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATR-Chk1 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [130] Unsal-Kacmaz K, Mullen TE, Kaufmann WK, Sancar A (2005) Coupling of human circadian and cell cycles by the timeless protein. Mol Cell Biol 25(8):3109–3116. doi: 10.1128/MCB.25.8.3109-3116.2005 source
- Not checked yetcites [131] Unsal-Kacmaz K, Chastain PD, Qu PP, Minoo P, Cordeiro-Stone M, Sancar A, Kaufmann WK (2007) The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement. Mol Cell Biol 27(8):3131–3142. doi: 10.1128/MCB.02190-06 source
- Not checked yetcites [132] Errico A, Costanzo V, Hunt T (2007) Tipin is required for stalled replication forks to resume DNA replication after removal of aphidicolin in Xenopus egg extracts. Proc Natl Acad Sci USA 104(38):14929–14934. doi: 10.1073/pnas.0706347104 source
- Not checked yetcites [133] Errico A, Costanzo V (2012) Mechanisms of replication fork protection: a safeguard for genome stability. Crit Rev Biochem Mol Biol 47(3):222–235. doi: 10.3109/10409238.2012.655374 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“ATMIN, an ATM interactor protein, was identified as an essential component in the ATM checkpoint pathway in response to oxidative stress. ATMIN mediates oxidative stress-induced ATM activity, thereby protecting the aging brain from accumulating DNA damage [78].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [78] Kanu N, Penicud K, Hristova M, Wong B, Irvine E, Plattner F, Raivich G, Behrens A (2010) The ATM cofactor ATMIN protects against oxidative stress and accumulation of DNA damage in the aging brain. J Biol Chem 285(49):38534–38542. doi: 10.1074/jbc.M110.145896 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Ochratoxin A, one of the most abundant mycotoxin food contaminants, induces oxidative DNA damage and triggers an ATM-dependent G2 arrest in human gastric epithelium GES-1 cells [72].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [72] Cui J, Liu J, Wu S, Wang Y, Shen H, Xing L, Wang J, Yan X, Zhang X (2013) Oxidative DNA damage is involved in ochratoxin A-induced G2 arrest through ataxia telangiectasia-mutated (ATM) pathways in human gastric epithelium GES-1 cells in vitro. Arch Toxicol 87(10):1829–1840. doi: 10.1007/s00204-013-1043-3 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“ATR was originally cloned as a member of the phosphoinositide 3-kinase–related kinase (PIKK) family and is essential for early embryonic development [32, 80, 81].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATR-Chk1 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [32] Cimprich KA, Cortez D (2008) ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9(8):616–627. doi: 10.1038/nrm2450 source
- Not checked yetcites [80] Cimprich KA, Shin TB, Keith CT, Schreiber SL (1996) cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein. Proc Natl Acad Sci USA 93(7):2850–2855 source
- Not checked yetcites [81] Brown EJ, Baltimore D (2000) ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev 14(4):397–402 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“As A-T fibroblast cells (ATM−/−) are more susceptible to oxidative stress than normal cells, ATM was proposed as a major sensor of oxidative DNA damage or ROS [73].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [73] Rotman G, Shiloh Y (1997) Ataxia-telangiectasia: is ATM a sensor of oxidative damage and stress? BioEssays 19(10):911–917. doi: 10.1002/bies.950191011 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The ATR-ATRIP complex and 9-1-1 complexes are recruited to RPA-ssDNA independently and are bridged by the multiple-function protein TopBP1 (Topoisomerase IIβ binding protein 1) [106–110].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATR-Chk1 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [106] Kondo T, Wakayama T, Naiki T, Matsumoto K, Sugimoto K (2001) Recruitment of Mec1 and Ddc1 checkpoint proteins to double-strand breaks through distinct mechanisms. Science 294(5543):867–870. doi: 10.1126/science.1063827 source
- Not checked yetcites [107] Melo JA, Cohen J, Toczyski DP (2001) Two checkpoint complexes are independently recruited to sites of DNA damage in vivo. Genes Dev 15(21):2809–2821. doi: 10.1101/gad.903501 source
- Not checked yetcites [108] Kanoh Y, Tamai K, Shirahige K (2006) Different requirements for the association of ATR-ATRIP and 9-1-1 to the stalled replication forks. Gene 377:88–95. doi: 10.1016/j.gene.2006.03.019 source
- Not checked yetcites [109] Garcia V, Furuya K, Carr AM (2005) Identification and functional analysis of TopBP1 and its homologs. DNA Repair (Amst) 4(11):1227–1239. doi: 10.1016/j.dnarep.2005.04.001 source
- Not checked yetcites [110] Sokka M, Parkkinen S, Pospiech H, Syvaoja JE (2010) Function of TopBP1 in genome stability. Subcell Biochem 50:119–141. doi: 10.1007/978-90-481-3471-7_7 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Hydrogen peroxide represses mTORC1 in a dose and time-dependent manner, and the mTORC1 repression by ROS requires the presence of ATM in the cytoplasm, suggesting a sub-cellular compartment requirement for ATM signaling in oxidative stress [77].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATM-Chk2 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [77] Alexander A, Cai SL, Kim J, Nanez A, Sahin M, MacLean KH, Inoki K, Guan KL, Shen J, Person MD, Kusewitt D, Mills GB, Kastan MB, Walker CL (2010) ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci USA 107(9):4153–4158. doi: 10.1073/pnas.0913860107 source
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None of the sources cited for this claim have been checked yet.
In the paper
“A long stretch of ssDNA can be generated through the functional uncoupling of minichromosome maintenance (MCM) helicase and DNA polymerase in DNA replication stress, the DSB end resection by DNA exonuclease such as CtIP in DSB response, the Exo1-mediated processing of NER intermediates after UV radiation, and the SSB end resection by AP endonuclease 2 (APE2) in oxidative stress [86, 97–99]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATR-Chk1 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [86] Willis J, Patel Y, Lentz BL, Yan S (2013) APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress. Proc Natl Acad Sci USA 110(26):10592–10597. doi: 10.1073/pnas.1301445110 source
- Not checked yetcites [97] Byun TS, Pacek M, Yee MC, Walter JC, Cimprich KA (2005) Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev 19(9):1040–1052. doi: 10.1101/gad.1301205 source
- Not checked yetcites [98] You Z, Shi LZ, Zhu Q, Wu P, Zhang YW, Basilio A, Tonnu N, Verma IM, Berns MW, Hunter T (2009) CtIP links DNA double-strand break sensing to resection. Mol Cell 36(6):954–969. doi: 10.1016/j.molcel.2009.12.002 source
- Not checked yetcites [99] Giannattasio M, Follonier C, Tourriere H, Puddu F, Lazzaro F, Pasero P, Lopes M, Plevani P, Muzi-Falconi M (2010) Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps, and promotes checkpoint activation. Mol Cell 40(1):50–62. doi: 10.1016/j.molcel.2010.09.004 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“UV-induced replication stress triggers ATM phosphorylation at Serine 1981, Chk2 phosphorylation at Threonine 68, and H2AX phosphorylation at Serine 139.”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Alternatively, in response to the DNA methylating agent temozolomide, the ATR-Chk1 checkpoint is activated to arrest cell cycle at G2/M transition. This is followed by ATM-Chk2 checkpoint activation, suggesting ATR functions earlier than ATM [143].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
What the sources say
- Not checked yetcites [143] Caporali S, Falcinelli S, Starace G, Russo MT, Bonmassar E, Jiricny J, D’Atri S (2004) DNA damage induced by temozolomide signals to both ATM and ATR: role of the mismatch repair system. Mol Pharmacol 66(3):478–491. doi: 10.1124/mol.66.3 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Additionally, an ATM-to-ATR switch during the biphasic DSB response was proposed in a report using mammalian cell lysates [141].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
What the sources say
- Not checked yetcites [141] Shiotani B, Zou L (2009) Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol Cell 33(5):547–558. doi: 10.1016/j.molcel.2009.01.024 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“ATM is essential for the recruitment of ATR to IR-damaged chromatin and Chk1 phosphorylation at Serine 345 [139].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
What the sources say
- Not checked yetcites [139] Cuadrado M, Martinez-Pastor B, Murga M, Toledo LI, Gutierrez-Martinez P, Lopez E, Fernandez-Capetillo O (2006) ATM regulates ATR chromatin loading in response to DNA double-strand breaks. J Exp Med 203(2):297–303. doi: 10.1084/jem.20051923 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“HNE also induces caffeine-sensitive ATR phosphorylation at Serine 428 and Chk1 phosphorylation at Serine 296 [147].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
What the sources say
- Not checked yetcites [147] Chaudhary P, Sharma R, Sahu M, Vishwanatha JK, Awasthi S, Awasthi YC (2013) 4-Hydroxynonenal induces G2/M phase cell cycle arrest by activation of the ataxia telangiectasia mutated and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) signaling pathway. J Biol Chem 288(28):20532–20546. doi: 10.1074/jbc.M113.467662 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, there is a suggestion of crosstalk and transition between these two pathways.”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“It was proposed recently that DDR kinases promote efficient DNA repair by directly regulating the DNA repair machinery, changing the local chromatin environment and cellular environment [166].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
What the sources say
- Not checked yetcites [166] Sirbu BM, Cortez D (2013) DNA damage response: three levels of DNA repair regulation. Cold Spring Harb Perspect Biol 5(8):a012724. doi: 10.1101/cshperspect.a012724 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Several studies support the role of ATM-Chk2 and ATR-Chk1 pathways for BER, NER, MMR and HR pathways in cellular response to oxidative stress; however, molecular mechanisms of how exactly DDR pathways regulate DNA repair pathways in oxidative stress require more clarity.”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“However, eliminating ATM kinase activity by its specific inhibitor KU55933 does not affect hydrogen peroxide-induced Chk1 phosphorylation, suggesting ATM may be nonessential for ATR-Chk1 checkpoint activation in oxidative stress response [86].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
What the sources say
- Not checked yetcites [86] Willis J, Patel Y, Lentz BL, Yan S (2013) APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress. Proc Natl Acad Sci USA 110(26):10592–10597. doi: 10.1073/pnas.1301445110 source
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings suggest that ATM and ATR may be activated sequentially, the order of which is dependent on the nature of DNA damage or stress (DSBs versus stalled replication forks or UV radiation), and that there is direct cross talk between the two key DDR kinases.”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Hydrogen peroxide triggers both ATM phosphorylation at Serine 1981 and Chk1 phosphorylation at Serine 344 in Xenopus egg extracts [86].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
What the sources say
- Not checked yetcites [86] Willis J, Patel Y, Lentz BL, Yan S (2013) APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress. Proc Natl Acad Sci USA 110(26):10592–10597. doi: 10.1073/pnas.1301445110 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Artesunate can cause oxidative DNA damage and trigger the phosphorylation of ATM, Chk2, Chk1, and H2AX, and eventually may lead to apoptosis in human glioblastoma cells [25].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
What the sources say
- Not checked yetcites [25] Berdelle N, Nikolova T, Quiros S, Efferth T, Kaina B (2011) Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells. Mol Cancer Ther 10(12):2224–2233. doi: 10.1158/1535-7163.MCT-11-0534 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“TDP1 protects against oxidative DNA damage and has been implicated in SSBR [169].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
What the sources say
- Not checked yetcites [169] Meagher M, Lightowlers RN (2014) The role of TDP1 and APTX in mitochondrial DNA repair. Biochimie 100:121–124. doi: 10.1016/j.biochi.2013.10.011 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, the natural antioxidant Lycopene inhibits H. pylori-induced gastric diseases associated with oxidative DNA damage (e.g., 8–OH–G and DSBs) and prevents ROS-induced ATM- and ATR-mediated DDR in gastric epithelial AGS cells [138].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATR-Chk1 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [138] Jang SH, Lim JW, Morio T, Kim H (2012) Lycopene inhibits Helicobacter pylori-induced ATM/ATR-dependent DNA damage response in gastric epithelial AGS cells. Free Radic Biol Med 52(3):607–615. doi: 10.1016/j.freeradbiomed.2011.11.010 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The selenium compound and its metabolites (e.g., Na2SeO3, MSeA, or MSeC) induce ROS, such as 8-oxo-G, and cause MLH1-mediated and G2/M arrest in HCT116 [172].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
What the sources say
- Not checked yetcites [172] Qi Y, Schoene NW, Lartey FM, Cheng WH (2010) Selenium compounds activate ATM-dependent DNA damage response via the mismatch repair protein hMLH1 in colorectal cancer cells. J Biol Chem 285(43):33010–33017. doi: 10.1074/jbc.M110.137406 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“4-Hydroxynonenal (HNE)-induced DSBs enhance comet tail formation and H2AX phosphorylation in hepatocellular carcinoma cells, suggesting ATM activation [147–149].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
What the sources say
- Not checked yetcites [147] Chaudhary P, Sharma R, Sahu M, Vishwanatha JK, Awasthi S, Awasthi YC (2013) 4-Hydroxynonenal induces G2/M phase cell cycle arrest by activation of the ataxia telangiectasia mutated and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) signaling pathway. J Biol Chem 288(28):20532–20546. doi: 10.1074/jbc.M113.467662 source
- Not checked yetcites [148] Ward IM, Chen J (2001) Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 276(51):47759–47762. doi: 10.1074/jbc.C100569200 source
- Not checked yetcites [149] Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ (2001) ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 276(45):42462–42467. doi: 10.1074/jbc.C100466200 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“More recently, it has been demonstrated that hydrogen peroxide triggers ATR-Chk1 checkpoint signaling in human dermal fibroblasts HDF cells [137] and in Xenopus egg extracts [86].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > ATR-Chk1 checkpoint activation in oxidative stress
What the sources say
- Not checked yetcites [137] Yang Y, Durando M, Smith-Roe SL, Sproul C, Greenwalt AM, Kaufmann W, Oh S, Hendrickson EA, Vaziri C (2013) Cell cycle stage-specific roles of Rad18 in tolerance and repair of oxidative DNA damage. Nucleic Acids Res 41(4):2296–2312. doi: 10.1093/nar/gks1325 source
- Not checked yetcites [86] Willis J, Patel Y, Lentz BL, Yan S (2013) APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress. Proc Natl Acad Sci USA 110(26):10592–10597. doi: 10.1073/pnas.1301445110 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Furthermore, ATM is essential for DSB-induced ATR activation in the S and G2 phases of cell cycle, but not in the G1 phase [140].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > DNA damage response pathways in oxidative stress > Crosstalk between ATM-Chk2 and ATR-Chk1 pathways
What the sources say
- Not checked yetcites [140] Jazayeri A, Falck J, Lukas C, Bartek J, Smith GC, Lukas J, Jackson SP (2006) ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 8(1):37–45. doi: 10.1038/ncb1337 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Cisplatin-induced nuclear import of XPA is also dependent on an ATR checkpoint in p53-proficient, but not p53-deficient, lung cancer cells [191]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
What the sources say
- Not checked yetcites [191] Li Z, Musich PR, Zou Y (2011) Differential DNA damage responses in p53 proficient and deficient cells: cisplatin-induced nuclear import of XPA is independent of ATR checkpoint in p53-deficient lung cancer cells. Int J Biochem Mol Biol 2(2):138–145
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“ATM is essential for MLH1 phosphorylation at Serine 406 and its stability following chemotherapy drug doxorubicin treatment, suggesting the regulation of MMR proteins by ATM [173].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
What the sources say
- Not checked yetcites [173] Romeo F, Falbo L, Di Sanzo M, Misaggi R, Faniello MC, Viglietto G, Cuda G, Costanzo F, Quaresima B (2011) BRCA1 is required for hMLH1 stabilization following doxorubicin-induced DNA damage. Int J Biochem Cell Biol 43(12):1754–1763. doi: 10.1016/j.biocel.2011.08.011 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Moreover, ATM plays an important role for the recruitment of Ku complex to hydrogen peroxide-damaged chromatin, further supporting the role of ATM in DSB repair by NHEJ [174, 175] (Fig. 6).”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
What the sources say
- Not checked yetcites [174] Lee JH, Kim KH, Morio T, Kim H (2006) Ataxia-telangiectasia-mutated-dependent activation of Ku in human fibroblasts exposed to hydrogen peroxide. Ann NY Acad Sci 1091:76–82. doi: 10.1196/annals.1378.056 source
- Not checked yetcites [175] Kuhne C, Tjornhammar ML, Pongor S, Banks L, Simoncsits A (2003) Repair of a minimal DNA double-strand break by NHEJ requires DNA-PKcs and is controlled by the ATM/ATR checkpoint. Nucleic Acids Res 31(24):7227–7237 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In response to UV damage, ATR phosphorylates XPA at Serine 196 and regulates the nuclear import of XPA”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
What the sources say
- Not checked yetcites [187] Wu X, Shell SM, Yang Z, Zou Y (2006) Phosphorylation of nucleotide excision repair factor xeroderma pigmentosum group A by ataxia telangiectasia mutated and Rad3-related-dependent checkpoint pathway promotes cell survival in response to UV irradiation. Cancer Res 66(6):2997–3005. doi: 10.1158/0008-5472.CAN-05-3403 source
- Not checked yetcites [188] Wu X, Shell SM, Liu Y, Zou Y (2007) ATR-dependent checkpoint modulates XPA nuclear import in response to UV irradiation. Oncogene 26(5):757–764. doi: 10.1038/sj.onc.1209828 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“DDB2 and XPC recruit ATM and ATR to UV-damaged sites and promote ATM-Chk2 and ATR-Chk1 checkpoint signaling.”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [202] Marti TM, Hefner E, Feeney L, Natale V, Cleaver JE (2006) H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks. Proc Natl Acad Sci USA 103(26):9891–9896. doi: 10.1073/pnas.0603779103 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“MMS induces unresolved BER intermediates in XRCC1-deficient cells and activates ATM and ATR-dependent DDR pathways, including S-phase delay and SMC1 (structural maintenance of chromosomes protein 1) phosphorylation at Serine 966 and Chk1 phosphorylation at Serine 345 [199]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [199] Brem R, Fernet M, Chapot B, Hall J (2008) The methyl methanesulfonate induced S-phase delay in XRCC1-deficient cells requires ATM and ATR. DNA Repair (Amst) 7(6):849–857. doi: 10.1016/j.dnarep.2008.02.002 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“DNA repair proteins (such as DNA nucleases) may process DNA damage into structures for DDR protein recruitment or recruit DDR proteins to damaged sites via direct protein–protein interactions.”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [99] Giannattasio M, Follonier C, Tourriere H, Puddu F, Lazzaro F, Pasero P, Lopes M, Plevani P, Muzi-Falconi M (2010) Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps, and promotes checkpoint activation. Mol Cell 40(1):50–62. doi: 10.1016/j.molcel.2010.09.004 source
- Not checked yetcites [196] Brown KD, Rathi A, Kamath R, Beardsley DI, Zhan Q, Mannino JL, Baskaran R (2003) The mismatch repair system is required for S-phase checkpoint activation. Nat Genet 33(1):80–84. doi: 10.1038/ng1052 source
- Not checked yetcites [197] Yoshioka K, Yoshioka Y, Hsieh P (2006) ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Mol Cell 22(4):501–510. doi: 10.1016/j.molcel.2006.04.023 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Notably, ATM is required for the selenium-induced MLH1-PMS2 association, which is essential for the repair efficiency [172] (Fig. 5).”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
What the sources say
- Not checked yetcites [172] Qi Y, Schoene NW, Lartey FM, Cheng WH (2010) Selenium compounds activate ATM-dependent DNA damage response via the mismatch repair protein hMLH1 in colorectal cancer cells. J Biol Chem 285(43):33010–33017. doi: 10.1074/jbc.M110.137406 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Importantly, the recruitment of the 9-1-1 complex to H2O2-damaged chromatin requires APE2-mediated generation of RPA-ssDNA, suggesting the 9-1-1 complex may promote the BER pathway via a positive feedback mechanism [86].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DDR pathways affect DNA repair pathways
What the sources say
- Not checked yetcites [86] Willis J, Patel Y, Lentz BL, Yan S (2013) APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress. Proc Natl Acad Sci USA 110(26):10592–10597. doi: 10.1073/pnas.1301445110 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“suggesting that GG-NER but not TC-NER (transcription-coupled NER) is required for ATR-Chk1 checkpoint signaling [200]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [200] Marini F, Nardo T, Giannattasio M, Minuzzo M, Stefanini M, Plevani P, Muzi Falconi M (2006) DNA nucleotide excision repair-dependent signaling to checkpoint activation. Proc Natl Acad Sci USA 103(46):17325–17330. doi: 10.1073/pnas.0605446103 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“ATM and ATR seem to be not essential for the recruitment of DDB2 and XPC to UV-damage sites and the NER repair of CPD and 6–4PP [203]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [203] Ray A, Milum K, Battu A, Wani G, Wani AA (2013) NER initiation factors, DDB2 and XPC, regulate UV radiation response by recruiting ATR and ATM kinases to DNA damage sites. DNA Repair (Amst) 12(4):273–283. doi: 10.1016/j.dnarep.2013.01.003 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The interactions between MMR and DDR proteins (i.e., MSH2-Chk2 and MLH1-ATM) promote the recruitment of DDR proteins to IR-damaged sites and facilitate Chk2 phosphorylation by ATM [196]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [196] Brown KD, Rathi A, Kamath R, Beardsley DI, Zhan Q, Mannino JL, Baskaran R (2003) The mismatch repair system is required for S-phase checkpoint activation. Nat Genet 33(1):80–84. doi: 10.1038/ng1052 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The MRN complex is required for the activation of ATM and ATR-dependent DDR pathways in response to DSBs and stalled DNA replication forks, respectively [57, 125, 218].”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [57] Lee JH, Paull TT (2004) Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304(5667):93–96. doi: 10.1126/science.1091496 source
- Not checked yetcites [125] Duursma AM, Driscoll R, Elias JE, Cimprich KA (2013) A role for the MRN complex in ATR activation via TOPBP1 recruitment. Mol Cell 50(1):116–122. doi: 10.1016/j.molcel.2013.03.006 source
- Not checked yetcites [218] Williams RS, Williams JS, Tainer JA (2007) Mre11-Rad50-Nbs1 is a keystone complex connecting DNA repair machinery, double-strand break signaling, and the chromatin template. Biochem Cell Biol 85(4):509–520. doi: 10.1139/O07-069 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Exo1 localizes with XPA to damage sites after local UV irradiation in non-replicating cells and converts NER intermediates into ssDNA to promote DDR signaling [99, 205]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [99] Giannattasio M, Follonier C, Tourriere H, Puddu F, Lazzaro F, Pasero P, Lopes M, Plevani P, Muzi-Falconi M (2010) Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps, and promotes checkpoint activation. Mol Cell 40(1):50–62. doi: 10.1016/j.molcel.2010.09.004 source
- Not checked yetcites [205] Sertic S, Pizzi S, Cloney R, Lehmann AR, Marini F, Plevani P, Muzi-Falconi M (2011) Human exonuclease 1 connects nucleotide excision repair (NER) processing with checkpoint activation in response to UV irradiation. Proc Natl Acad Sci USA 108(33):13647–13652. doi: 10.1073/pnas.1108547108 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“MutSα specifically recognizes O6-meG:T mismatch, but not O6-meG:C”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [197] Yoshioka K, Yoshioka Y, Hsieh P (2006) ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Mol Cell 22(4):501–510. doi: 10.1016/j.molcel.2006.04.023 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“XPC and XPG are essential for the recruitment of ATM to damage sites after cisplatin treatment, preventing cisplatin-induced apoptosis [204]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [204] Colton SL, Xu XS, Wang YA, Wang G (2006) The involvement of ataxia-telangiectasia mutated protein activation in nucleotide excision repair-facilitated cell survival with cisplatin treatment. J Biol Chem 281(37):27117–27125. doi: 10.1074/jbc.M602826200 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“SN1-type DNA alkylating agents induce DNA adducts, such as O6-meG (O6-methylguanine), and activate the ATR-Chk1 pathway.”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [197] Yoshioka K, Yoshioka Y, Hsieh P (2006) ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Mol Cell 22(4):501–510. doi: 10.1016/j.molcel.2006.04.023 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“FdU may be excised by the uracil glycosylase Smug1 to protect cells from death [210, 211]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [210] Longley DB, Harkin DP, Johnston PG (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3(5):330–338. doi: 10.1038/nrc1074 source
- Not checked yetcites [211] An Q, Robins P, Lindahl T, Barnes DE (2007) 5-Fluorouracil incorporated into DNA is excised by the Smug1 DNA glycosylase to reduce drug cytotoxicity. Cancer Res 67(3):940–945. doi: 10.1158/0008-5472.CAN-06-2960 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“MutSα associates with ATR, TopBP1, Claspin, and Chk1 (but not Rad17, Rad9, or RPA), whereas MutLα interacts only with TopBP1 and Claspin [214]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [214] Liu Y, Fang Y, Shao H, Lindsey-Boltz L, Sancar A, Modrich P (2010) Interactions of human mismatch repair proteins MutSalpha and MutLalpha with proteins of the ATR-Chk1 pathway. J Biol Chem 285(8):5974–5982. doi: 10.1074/jbc.M109.076109 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“MSH2 binds to Chk2 and that MLH1 associates with ATM”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [196] Brown KD, Rathi A, Kamath R, Beardsley DI, Zhan Q, Mannino JL, Baskaran R (2003) The mismatch repair system is required for S-phase checkpoint activation. Nat Genet 33(1):80–84. doi: 10.1038/ng1052 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CtIP is required for DSB end resection, the recruitment of RPA and ATR to DSBs, and subsequent ATR activation [98, 220]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
What the sources say
- Not checked yetcites [98] You Z, Shi LZ, Zhu Q, Wu P, Zhang YW, Basilio A, Tonnu N, Verma IM, Berns MW, Hunter T (2009) CtIP links DNA double-strand break sensing to resection. Mol Cell 36(6):954–969. doi: 10.1016/j.molcel.2009.12.002 source
- Not checked yetcites [220] Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP (2007) Human CtIP promotes DNA end resection. Nature 450(7169):509–514. doi: 10.1038/nature06337 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“factors involved in DNA repair and DDR pathways have become therapeutic targets and are currently being tested in both laboratory and clinical studies [151, 222]”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Concluding remarks
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, in response to DSBs, ATM may be recruited to the DSB end by the MRN complex and other proteins for activation, whereas ATR is activated after DSB end resection by enzymes such as CtIP and Exo1”
§ Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress > Functional interplay between DNA damage response pathways and DNA repair pathways in oxidative stress > DNA repair proteins are important for DNA damage response in oxidative stress
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“With the recognized knowledge that Aβ induces oxidative DNA damage (Suberbielle et al., 2013; Wu et al., 2014; Yan et al., 2014)”
From CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer’s Disease (2018) · cites this paper as Yan et al., 2014
Experimental — accuracy not yet measured
Citations
Cites
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Metadata
- Authors
- Yan, S., Sorrell, M., & Berman, Z.
- Affiliations
- University of North Carolina at Charlotte (US)
- Corresponding author
- Yan, Shan
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2014-06-20
- Volume
- 71
- Issue
- 20
- Pages
- 3951-3967
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC4176976
- OpenAlex
- W2033918102
- Semantic Scholar
- c1f29eae29590d9aed98dbf27ad4dedb7b0e0a1b
- Cited by
- 247
- References
- 225
- Citations by year
- 2026: 23 · 2025: 11 · 2024: 24 · 2023: 11 · 2022: 32 · 2021: 26 · 2020: 25 · 2019: 22 · 2018: 23 · 2017: 18 · 2016: 16 · 2015: 14 · 2014: 2
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R15GM101571)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- DNA damage response, DNA repair pathways, oxidative DNA damage, oxidative stress, genome stability, cell cycle checkpoints, apoptosis, cellular senescence, cancer, neurodegenerative diseases
- MeSH terms
- Checkpoint Kinase 1, DNA Damage, DNA Repair, DNA-Binding Proteins, Humans, Protein Kinases, Signal Transduction, Oxidative Stress, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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