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Cited by 1,075DNA Repair MechanismsEffects of Radiation ExposureDNA and Nucleic Acid Chemistry

Requirement of the MRN complex for ATM activation by DNA damage

Open access
Uziel, Tamar, Lerenthal, Yaniv, Moyal, Lilach, Andegeko, Yair, Mittelman, Leonid, Shiloh, Yosef·2003·The EMBO Journal
DOI 10.1093/emboj/cdg541PMC PMC213795
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Abstract

The ATM protein kinase is a primary activator of the cellular response to DNA double-strand breaks (DSBs). In response to DSBs, ATM is activated and phosphorylates key players in various branches of the DNA damage response network. ATM deficiency causes the genetic disorder ataxia-telangiectasia (A-T), characterized by cerebellar degeneration, immunodeficiency, radiation sensitivity, chromosomal instability and cancer predisposition. The MRN complex, whose core contains the Mre11, Rad50 and Nbs1 proteins, is involved in the initial processing of DSBs. Hypomorphic mutations in the NBS1 and MRE11 genes lead to two other genomic instability disorders: the Nijmegen breakage syndrome (NBS) and A-T like disease (A-TLD), respectively. The order in which ATM and MRN act in the early phase of the DSB response is unclear. Here we show that functional MRN is required for ATM activation, and consequently for timely activation of ATM-mediated pathways. Collectively, these and previous results assign to components of the MRN complex roles upstream and downstream of ATM in the DNA damage response pathway and explain the clinical resemblance between A-T and A-TLD.

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Crossref · 10.1093/emboj/cdg541

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 53 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Defective phosphorylation of ATM targets in MRN-de®cient cells

    All three ATM-dependent phosphorylations examined (Chk2, p53 Ser15, Hdm2 Ser395) decline progressively in A-TLD cells as Mre11 deficiency increases, regardless of Nbs1 dependence.

    “Signi®cantly, all three phosphorylations were increasingly reduced in A-TLD cells in correlation with the degree of Mre11 de®ciency, regardless of their dependence on Nbs1 (Figure 4).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Discussion

    Bound ATM is autophosphorylated, i.e., activated.

    “We noticed that, indeed, bound ATM is autophosphorylated, i.e., activated.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Discussion

    Not every ATM substrate requires Nbs1 for its phosphorylation.

    “We showed here, however, that not every substrate of ATM requires Nbs1 for its phosphorylation.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Nuclear retention of ATM is defective in cells with MRN de®ciencies

    Nuclear retention of ATM after radiomimetic damage is increasingly attenuated in NBS, A-TLD(M), and A-TLD(S) cells.

    “Nuclear retention of ATM following radiomimetic damage was increasingly attenuated in NBS, A-TLD(M) and A-TLD(S) (Figure 3).”
    Quote in the paperSubstantial claim
  • Findingcitation
    § Reconstitution of the MRN complex restores ATM activation

    In NBS cells reconstituted with Nbs1, the attenuation in ATM activation typical of parental NBS cells disappears.

    “Indeed, the attenuation in ATM activation typical of the parental NBS cells disappeared in the reconstituted cells (Figure 6C).”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 12

  • May combine two claims.

    Findingown data
    § Defective phosphorylation of ATM targets in MRN-de®cient cells

    Quantitation of the ATM phosphorylation motif response is significantly impaired in A-TLD(M), abolished in A-TLD(S), and variably low in NBS.

    “Quantitation of this response indicated that it is signi®cantly impaired in A-TLD(M) cells and abolished in A-TLD(S) cells, while being variably low in NBS cells (Figure 5B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Reconstitution of the MRN complex restores ATM activation

    In A-TLD(S) cells, Mre11 expression restores normal amounts and nuclear co-localization of Rad50 and Nbs1, indicating reassembly of the nuclear MRN complex.

    “Mre11 expression reconstituted the normal levels and nuclear co-localization of Rad50 and Nbs1 (Figure 6A), suggesting reassembly of nuclear MRN complex.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § ATM activation is defective in cells with MRN de®ciencies

    After NCS, ATM autophosphorylation on Ser1981 is retarded in NBS cells, more moderately reduced in A-TLD(M), and most severely affected in A-TLD(S).

    “Dose response and time course experiments (Figure 2) indicated that ATM activation was indeed retarded in NBS cells, was more pronouncedly moderate in A-TLD(M), and most severely affected in A-TLD(S).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § ATM activation is defective in cells with MRN de®ciencies

    In vitro NCS-induced ATM kinase activity is moderately reduced in A-TLD(M) cells, abolished in A-TLD(S) cells, and variable/not significantly different from wild-type in NBS cells.

    “We noticed that the elevation in ATM's catalytic activity following NCS treatment was moderately reduced in A-TLD(M) cells and completely abolished in A-TLD(S) cells, while NBS cells exhibited variable extents of reduction in ATM activation, which on the average did not differ signi®cantly from those of wild-type cells (data not shown).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Reconstitution of the MRN complex restores ATM activation

    ATM activation and downstream substrate phosphorylation are reconstituted after Mre11 expression in A-TLD(S) cells.

    “Importantly, ATM activation (Figure 6B) and phosphorylation of downstream substrates (not shown) were subsequently reconstituted.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Nuclear retention of ATM is defective in cells with MRN de®ciencies

    Both retained and soluble ATM fractions contain activated ATM molecules.

    “Indeed, we noticed that both of the retained and soluble ATM fractions contained activated ATM molecules (Supplementary ®gure 1, available at The EMBO Journal Online).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Defective phosphorylation of ATM targets in MRN-de®cient cells

    After NCS exposure, an antibody recognizing ATM phosphorylation motifs produces a strong nuclear signal that depends on ATM in multiple cell lines.

    “Upon NCS treatment, this antibody reveals a strong, ATM-dependent nuclear response in a variety of cell lines (Figure 5A).”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data
    § Discussion

    The Mre11-3 mutant restores endogenous Rad50 and Nbs1 levels and nuclear localization.

    “Note reconstitution of endogenous Rad50 and Nbs1 levels and nuclear localization.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    The nuclear retention process is impaired to different degrees in A-TLD and NBS cells, most severely in the severe A-TLD variant.

    “This process is impaired to different extents in A-TLD and NBS cells, most seriously in the severe A-TLD variant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    Chk2 phosphorylation is delayed and reduced in A-TLD(M) cells.

    “the delayed and reduced phosphorylation of Chk2 in A-TLD(M) cells”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    In untreated cells most nuclear ATM is extracted and washed out, whereas NCS treatment makes a significant portion of nuclear ATM resistant to extraction.

    “In untreated cells most of the nuclear content of ATM is extracted and washed out, while prior NCS treatment (50 ng/ ml) renders a signi®cant portion of nuclear ATM extraction-resistant.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § Discussion

    The phosphorylation response is confined to the nucleus.

    “Phase contrast images of the cells indicate that this response is con®ned to the nucleus.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    Thirty minutes after NCS treatment, wild-type cells show a vigorous response while A-T cells show barely changed diffuse background staining.

    “Thirty minutes following NCS treatment, a vigorous response is observed in wild-type cells while the diffuse background staining in A-T cells is barely changed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Abstract

    Hypomorphic mutations in NBS1 and MRE11 cause Nijmegen breakage syndrome and A-T like disease, respectively.

    “Hypomorphic mutations in the NBS1 and MRE11 genes lead to two other genomic instability disorders: the Nijmegen breakage syndrome (NBS) and A-T like disease (A-TLD), respectively.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Digweed et al., 1999 source

      Not checked in the free run.

    • cites Tauchi et al., 2002 source

      Not checked in the free run.

    • cites Stewart et al., 1999 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Introduction

    The MRN complex participates in initial processing of DNA double-strand breaks through nuclease activity and DNA binding.

    “The MRN complex is involved in the initial processing of DSBs due to its nuclease activity and DNA binding capability (Petrini et al., 2001;D'Amours and Jackson, 2002).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Petrini et al., 2001

      Not checked in the free run.

    • cites D'Amours and Jackson, 2002 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Abstract

    ATM loss leads to ataxia-telangiectasia, marked by cerebellar degeneration, immune deficiency, radiosensitivity, chromosome instability, and a predisposition to cancer.

    “ATM de®ciency causes the genetic disorder ataxia-telangiectasia (A-T), characterized by cerebellar degeneration, immunode®ciency, radiation sensitivity, chromosomal instability and cancer predisposition.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Crawford, 1998 source

      Not checked in the free run.

    • cites Gatti et al., 2001 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data
    § Reconstitution of the MRN complex restores ATM activation

    Mre11's nuclease function is needed for correct ATM activation, and assembling the MRN complex alone does not suffice.

    “Interestingly, expression of the the Mre11-3 mutant protein in A-TLD(S) cells seemed to reconstitute nuclear MRN complex similarly to wild-type Mre11(Figure 7A), but failed to fully restore damage-induced ATM activation (Figure 7B).”
    • Also stated in: § Reconstitution of the MRN complex restores ATM activation · hedged
      “This result suggested to us that the mere assembly of the MRN complex is not suf®cient for proper ATM activation, and its nuclease activity, which resides in the Mre11 protein, is speci®cally required for this process.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § ATM activation is defective in cells with MRN de®ciencies

    ATM activation involves intermolecular autophosphorylation on Ser1981.

    “Bakkenist and Kastan (2003) have recently shown, however, that the damage-induced increase in ATM's kinase activity in vitro is just a modest re¯ection of the actual activation of ATM in cells, and demonstrated that this activation involves intermolecular autophosphorylation of ATM on Ser1981.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bakkenist and Kastan, 2003 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data
    § Abstract

    Functional MRN complex in the nucleus is required for proper ATM activation and for timely activation of ATM-mediated pathways.

    “Here we show that functional MRN is required for ATM activation, and consequently for timely activation of ATM-mediated pathways.”
    • Also stated in: § Reconstitution of the MRN complex restores ATM activation · plain
      “We concluded from these results that the presence of functional MRN complex in the nucleus is required for proper ATM activation.”
    • Also stated in: § Discussion · plain
      “We conclude that functional MRN complex is necessary for proper ATM-mediated response to DSBs (Figure 8).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Discussion

    ATM-mediated phosphorylation of Chk2 occurs specifically and exclusively at damaged sites.

    “The demonstration of ATM-mediated phosphorylation of Chk2 speci®cally and exclusively at the damaged sites (Lukas et al., 2003) attests to the importance of the binding of ATM to these sites, which is re¯ected in the retention phenomenon (Andegeko et al., 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lukas et al., 2003 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data
    § Nuclear retention of ATM is defective in cells with MRN de®ciencies

    The ordering of genotypes by increasing effect on ATM activation and on ATM nuclear retention is similar, suggesting the two phenomena are parallel facets of ATM's DNA damage response.

    “Interestingly, the order in which the different genotypes increasingly affected ATM activation and retention was similar for both phenomena, suggesting that they re¯ect two parallel facets of ATM's response to DNA damage.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Discussion

    In budding yeast, damage-induced activation of Tel1p, phosphorylation of its downstream targets, and activation of cell cycle checkpoints depend on functional Mre11/Rad50/Xrs2 complex, specifically on Mre11 nuclease activity.

    “Indeed, in the budding yeast, damage-induced activation of ATM's ortholog, Tel1p, subsequent phosphorylation of its downstream targets, and activation of pertinent pathways such as the cell cycle checkpoints are dependent on functional Mre11/Rad50/ Xrs2 complex (the yeast ortholog of the mammalian MRN complex)Ðspeci®cally on the nuclease activity of Mre11 (D'Amours and Jackson, 2001;Grenon et al.,”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites D'Amours and Jackson, 2001 source

      Not checked in the free run.

    • cites Grenon et al., 2001 source

      Not checked in the free run.

    • cites Usui et al., 2001 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data
    § Defective phosphorylation of ATM targets in MRN-de®cient cells

    This antibody recognizes phosphorylated forms of certain established ATM targets, including p53 and Chk2, plus other substrates being studied.

    “It detects the phosphorylated forms of some known ATM substrates, such as p53 and Chk2, and several other substrates currently under investigation in our laboratory.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation
    § Reconstitution of the MRN complex restores ATM activation

    hTERT immortalization does not alter phenotypic characteristics associated with defective DNA damage response of A-T cells and A-TLD(M) cells.

    “It was previously shown that hTERT immortalization does not alter the phenotypic characteristics associated with the defective DNA damage response of A-T cells (Wood et al., 2001) and A-TLD(M) cells (Stracker et al., 2002).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Wood et al., 2001 source

      Not checked in the free run.

    • cites Stracker et al., 2002 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    Varied clinical phenotypes from Nbs1 versus Mre11 defects might arise from distinct functions of each protein and from how much the whole MRN complex is disabled by the particular hypomorphic mutation.

    “The different phenotypes associated with genetic Nbs1 and Mre11 de®ciencies may re¯ect speci®c roles of each of them in the damage response, as well as the extent to which the function of the entire MRN complex is impaired by the corresponding hypomorphic mutations.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Discussion

    Phosphorylated Nbs1 plays a separate role in activation of specific cell cycle checkpoints.

    “Moreover, phosphorylated Nbs1 plays a separate role in the activation of speci®c cell cycle checkpoints (Buscemi et al., 2001;Lim et al., 2000).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Buscemi et al., 2001 source

      Not checked in the free run.

    • cites Lim et al., 2000 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation
    § Discussion

    Early DNA damage response events might not form a simple linear hierarchy with one fixed place per protein.

    “The sequence of events at the early stage of the DNA damage response may not necessarily be a simple hierarchy in which each protein has a single position in the damage signaling cascade (Bradbury and Jackson, 2003;Petrini and Stracker, 2003).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Bradbury and Jackson, 2003 source

      Not checked in the free run.

    • cites Petrini and Stracker, 2003

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    Because the three core MRN proteins physically associate and cooperate functionally, losing even part of one can abolish the complex's activities.

    “Due to the physical association and functional cooperation between the three core components of the MRN complex, even partial loss of one of them leads to abrogation of the complex's functions.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Defective phosphorylation of ATM targets in MRN-de®cient cells

    ATM targets serine or threonine residues that are followed by glutamine, known as SQ/TQ motifs.

    “ATM phosphorylates serine or threonine residues followed by glutamine (`SQ' or `TQ' motifs) (Kim et al., 1999;O'Neill et al., 2000).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Kim et al., 1999 source

      Not checked in the free run.

    • cites O'Neill et al., 2000 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Reconstitution of the MRN complex restores ATM activation

    Ectopic Nbs1 expression in NBS cells leads to reassembly of nuclear MRN complex and restores ATM-mediated Chk2 phosphorylation.

    “In these cells too, ectopic expression of Nbs1 leads to reassembly of the MRN complex in the nucleus (Tauchi et al., 2001) and restores ATM-mediated Chk2 phosphorylation (Buscemi et al., 2001).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Tauchi et al., 2001 source

      Not checked in the free run.

    • cites Buscemi et al., 2001 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Discussion

    The MRN complex forms two types of nuclear foci in response to DNA double-strand breaks: a rapid ATM-independent type and a prolonged ATM-dependent type.

    “Indeed, in response to DSBs, the MRN complex forms two types of nuclear foci: the ®rst is rapid and ATM-independent and probably re¯ects its sensor mode of action, while the second is ATM-dependent and prolonged and probably corresponds to MRN's downstream roles (Mirzoeva and Petrini, 2001;Mirzoeva and Petrini, 2003).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Mirzoeva and Petrini, 2001 source

      Not checked in the free run.

    • cites Mirzoeva and Petrini, 2003

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given
    § Discussion

    Low treatment doses are more likely to reflect physiological conditions and to explain human phenotypes.

    “Presumably, however, the low treatment doses re¯ect more realistic physiological situations and better explain human phenotypes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning
    § Discussion

    Differences in treatment protocols may explain why A-TLD(S) cells showed an A-T-like phenotype in this study but a moderate cellular phenotype in other reports.

    “Thus, different treatment protocols may account for the discrepancy between the A-T-like phenotype of A-TLD(S) cells observed by us and the moderate cellular phenotype reported for these cells by Stewart et al. (1999) and Falck et al. (2002).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Stewart et al. (1999) source

      Not checked in the free run.

    • cites Falck et al. (2002) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    Phosphorylated Nbs1 promotes phosphorylation of some ATM substrates and contributes to cell cycle checkpoint activation.

    “Phosphorylated Nbs1 facilitates the phosphorylation of certain ATM substrates and plays a role in the activation of cell cycle checkpoint.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    Processed DNA lesions recruit and activate ATM, which then phosphorylates substrates including Nbs1 and Mre11.

    “Processed DNA lesions lead to the recruitment and activation of ATM, which in turn phosphorylates its substrates, among them Nbs1 and Mre11.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Discussion

    Phosphorylation of Hdm2 on Ser395 abolishes its immunoreactivity with monoclonal antibody 2A10, so it appears as loss of the Hdm2 band on immunoblots.

    “This phosphorylation abolishes the immunoreactivity of Hdm2 with the monoclonal antibody 2A10 and is therefore expressed as loss of the Hdm2 band on immunoblots(Khosravi et al., 1999).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Khosravi et al., 1999 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation
    § Discussion

    A constitutive damage response is occasionally seen in cells with defective damage response and reflects elevated basal levels of DNA damage.

    “This constitutive damage response is occasionally observed in cells with defective damage response and represents elevated basal levels of DNA damage(Gatei et al., 2001;Kamsler et al., 2001).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Gatei et al., 2001 source

      Not checked in the free run.

    • cites Kamsler et al., 2001

      Not checked in the free run.

37 of 37

  • The paper relies on this without support.

    It is not known whether ATM or MRN acts first after DSB formation.

    “The order in which ATM and the MRN complex act in the early phase of the DSB response is unclear.”

  • The paper relies on this without support.

    A-T and A-TLD are highly similar clinically, while NBS does not share cerebellar degeneration.

    “Importantly, while A-T and A-TLD are highly similar, NBS does not share the cerebellar degeneration typical of these diseases.”

  • The paper relies on this without support.

    A dose of 50 ng/ml NCS is approximately equivalent to 2 Gy of ionizing radiation.

    “a dose of 50 ng/ml of NCS is roughly equivalent to 2 Gy of ionizing radiation”
3 of 3

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Severe A-TLD fibroblast line has two identifiers

    Minor

    The cell-line list identifies the severe A-TLD fibroblasts as D6807, but the subsequent immortalization method identifies the severe A-TLD line as D6087. The text does not clarify whether these are different lines or a transposed identifier.

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Authors
Uziel, T., Lerenthal, Y., Moyal, L., Andegeko, Y., Mittelman, L., & Shiloh, Y.
Affiliations
Tel Aviv University (IL)
Corresponding author
Shiloh, Yosef
ORCID
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2003-10-15
Volume
22
Issue
20
Pages
5612-5621
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.1093/emboj/cdg541
PMC
PMC213795
OpenAlex
W2045526190
Cited by
1,075
References
68
Citations by year
2026: 10 · 2025: 22 · 2024: 32 · 2023: 29 · 2022: 44 · 2021: 37 · 2020: 49 · 2019: 36 · 2018: 45 · 2017: 39 · 2016: 36 · 2015: 45 · 2014: 50 · 2013: 54 · 2012: 50
FWCI
23.83
Type
journal article
Language
en
Open access
Licence
Locations
  • The EMBO Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS031763, R01NS31763)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
ATM kinase activation, MRN complex, MRE11, RAD50, NBS1, DNA double-strand breaks, DNA damage response, ataxia telangiectasia, Nijmegen breakage syndrome, ataxia-telangiectasia-like disorder, genomic instability, DNA end processing
MeSH terms
MRE11 Homologue Protein, Ataxia Telangiectasia, Cell Line, Cell Survival, DNA Damage, DNA-Binding Proteins, Gene Expression Regulation, Humans, Nuclear Proteins, Phosphorylation, Reference Values, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, Saccharomyces cerevisiae Proteins, Ataxia Telangiectasia Mutated Proteins

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