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Cited by 11DNA Repair MechanismsAcute Lymphoblastic Leukemia researchCancer-related Molecular Pathways

The Spi1/PU.1 transcription factor accelerates replication fork progression by increasing PP1 phosphatase in leukemia

Open access
Rimmelé, Pauline, Esposito, Michela, Delestré, Laure, Guervilly, Jean-Hugues, Ridinger-Saison, Maya, Despras, Emmanuelle, Moreau-Gachelin, Françoise, Rosselli, Filippo +1 more·2017·Oncotarget
DOI 10.18632/oncotarget.16183PMC PMC5514894
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Abstract

// Pauline Rimmelé 1, 2 , Michela Esposito 3, 4 , Laure Delestré 3, 4 , Jean-Hugues Guervilly 3, 5 , Maya Ridinger-Saison 1, 2 , Emmanuelle Despras 3, 5 , Françoise Moreau-Gachelin 1, 2 , Filippo Rosselli 3, 5 , Christel Guillouf 1, 2, 3, 4, 6 1 Institut Curie, Paris, France 2 Inserm U830, Paris, France 3 Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France 4 Inserm U1170, Villejuif, France 5 CNRS UMR8200, Equipe Labellisée La Ligue Contre Le Cancer, Villejuif, France 6 CNRS, Paris, France Correspondence to: Christel Guillouf, email: christel.guillouf@gustaveroussy.fr Keywords: DNA replication, leukemia, Spi1/PU.1 oncogene, CHK1, PP1 Received: January 31, 2017 Accepted: March 03, 2017 Published: March 14, 2017 ABSTRACT Oncogenes trigger replicative stress that can lead to genetic instability, which participates in cancer progression. Thus, determining how cells cope with replicative stress can help our understanding of oncogenesis and lead to the identification of new antitumor treatment targets. We previously showed that constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads to pre-leukemic cells that have a shortened S phase duration with an increased replication fork speed and increased mutability in the absence of DNA breaks. Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence that this is not due to negative control of its primary kinase ATR. Notably, we found that the expression of the CHK1 phosphatase PP1α is increased in Spi1/PU.1-overexpressing cells. By exogenously modulating its activity, we demonstrate that PP1α is required to maintain CHK1 in a dephosphorylated state and, more importantly, that it is responsible for the accelerated replication fork progression in Spi1/PU.1-overexpressing cells. These results identify a novel pathway by which an oncogene influences replication in the absence of DNA damage.

AI snapshot

Written from the paper’s full text.

TL;DR

Spi1/PU.1 overexpression in pre-leukemic cells lowers CHK1 Ser345 phosphorylation by increasing PP1α phosphatase, which accelerates replication fork progression and shortens S phase without DNA breaks. PP1α activity is necessary and sufficient for this replication phenotype.

Key findings

  • Spi1 down-regulation by doxycycline in TgSpi1 pre-leukemic cells increased CHK1 Ser345 phosphorylation, while increased Spi1 expression in human K562 cells decreased it. This was not due to altered ATR activity: RPA32 was not phosphorylated in Spi1-overexpressing cells, ATR siRNA did not reduce CHK1 phosphorylation, and the ATR inhibitor VE-822 did not abolish the Spi1-dependent difference.
  • PP1α protein increased about two-fold in TgSpi1 cells after 2 or 3 days of doxycycline-induced Spi1 down-regulation and was up-regulated proportionally to Spi1 in K562 cells. The PP1 inhibitor tautomycin dose-dependently increased p-CHK1, whereas the PP2A inhibitor okadaic acid did not.
  • PP1α overexpression (Myc-tagged PP1α clones 4C and 7B) prevented the doxycycline-induced increase in CHK1 phosphorylation and eliminated the Spi1-dependent shortening of S phase duration (Student’s t-test, *P* < 0.05).
  • PP1 inhibition with tautomycin delayed S phase progression and significantly reduced replication fork speed (Mann-Whitney test, *P* < 0.0001), with strong G2 arrest at T0 (12% vs. 24% and 11% vs. 22% for shSpi1-A2B and shSpi1-A2C, respectively).

Methods

  • Mouse TgSpi1 pre-leukemic cells with doxycycline-inducible anti-Spi1 shRNAs (shSpi1-A2B and shSpi1-A2C) and human K562 leukemic cells with modulated Spi1 expression were cultured with Epo or SCF.
  • Immunoblotting measured phospho-CHK1 Ser345, PP1α, PP2A, ATR, RPA32, and related proteins; PP1/PP2A inhibitors, ATR siRNA, VE-822, and Myc-tagged PP1α overexpression were used to test pathway causality.
  • S phase duration was measured by BrdU relative movement flow cytometry; replication fork speed was measured by DNA fiber assays with sequential CldU/BrdU labeling; statistical comparisons used Student’s t-test and Mann-Whitney test.

Limitations

  • The paper states that tautomycin caused a strong G2 arrest, so the precise length of S phase could not be calculated; CHK1 inhibition triggered fast G1 arrest and cell death, preventing direct testing of whether low CHK1 activity accelerates fork elongation.
  • The paper states that how Spi1 controls PP1α steady-state levels remains an open question, and that transcriptional regulation, proteasomal degradation, and lysosomal degradation were excluded.
  • The text makes evident that the findings rely on murine TgSpi1 pre-leukemic cells and K562 human leukemic cell lines, not primary AML samples, and no in vivo leukemic progression experiment is reported here.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.18632/oncotarget.16183

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

6 of 28 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Most oncogenes cause replication stress by increasing origin firing and triggering DNA damage.

    “Indeed, most oncogenes that have been studied in the literature cause replication stress by increasing origin firing and triggering DNA damage [12, 29]”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [12] d’Adda di Fagagna, 2006, Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication, Nature source
    • cites [29] Kerem, 2011, Nucleotide deficiency promotes genomic instability in early stages of cancer development, Cell source

      The Results section reports that HPV-16 E6/E7 expression increased the number of active replication origins, and the Discussion links E6/E7 and cyclin E to replication stress and DNA damage. The paper studies these particular oncogenes, not most oncogenes studied in the literature. It also identifies an insufficient nucleotide pool, rather than increased origin firing, as the basis of the replication stress it investigated. Page numbers are not available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Findingown data

    In Spi1-overexpressing pre-leukemic and K562 cells, CHK1 phosphorylation at Ser345 is decreased compared to cells with low Spi1 expression.

    “Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence that this is not due to negative control of its primary kinase ATR.”
    • Also stated in: § Spi1 overexpression reduces CHK1 phosphorylation in pre-leukemic cells · boosted
      “Dox-induced Spi1 down-regulation in both shSpi1-A2B and shSpi1-A2C cells was accompanied by a clear increase in CHK1 Ser345 phosphorylation (Figure 1).”
    • Also stated in: § Spi1 overexpression reduces CHK1 phosphorylation in pre-leukemic cells · plain
      “Likewise, in human K562 cells, increasing Spi1 expression resulted in decreased CHK1 phosphorylation (Figure 1D).”
    Quote in the paperSubstantial claim
  • Findingown data

    Decrease of ATR by siRNA in Spi1-silenced cells did not reduce CHK1 phosphorylation.

    “Indeed, we found that decrease of ATR by siRNA in Spi1-silenced cells did not reduce CHK1 phosphorylation or the cell cycle.”
    Quote in the paperSubstantial claim
  • Findingown data

    PP1 activity is necessary to mediate Spi1 effect on acceleration of DNA replication and S phase duration.

    “Two functional assays using overexpression of the PP1α catalytic subunit or inhibition of its activity show that PP1 activity is sufficient and necessary to mediate Spi1 effect on acceleration of DNA replication and S phase duration.”
    Quote in the paperSubstantial claim
  • Findingown data

    The tautomycin-induced decrease in fork elongation is dose-dependent.

    “Interestingly, the tautomycin-induced decrease in fork elongation was dose-dependent, as was CHK1 phosphorylation (Figure 3A).”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 12
  • May combine two claims. 17

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

    Premisecitation

    A role for PP1 in dephosphorylating CHK1 has been proposed for the recovery of DNA damage G2 checkpoint arrest in yeast.

    “A role for PP1 in dephosphorylating CHK1 has been proposed for the recovery of DNA damage G2 checkpoint arrest in yeast [22].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [22] O’Connell, 2004, Recovery from DNA damage checkpoint arrest by PP1-mediated inhibition of Chk1, Embo J source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In response to camptothecin, inhibition of CHK1 accelerates both the speed of replication fork elongation and origin firing.

    “However, in response to camptothecin, inhibition of CHK1 accelerates both the speed of replication fork elongation and origin firing [35, 36].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [35] Pommier, 2007, The intra-S phase checkpoint affects both DNA replication initiation and elongation: single-cell and -DNA fiber analyses, Molecular and cellular biology source
    • cites [36] Pommier, 2014, The ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase I inhibitors by disabling DNA replication initiation and fork elongation responses, Cancer research

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Several oncogenic steps are involved in this leukemic model, which were associated with the acquisition of de novo genetic alterations.

    “This is particularly relevant in this leukemic model, as we have previously demonstrated the involvement of several oncogenic steps, which were associated with the acquisition of de novo genetic alterations [6].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [6] Moreau-Gachelin, 2005, Kit-activating mutations cooperate with Spi1/PU.1 overexpression to promote tumorigenic progression during erythroleukemia in mice, Cancer Cell source

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

    Premisecitation

    CHK1 inhibition slows replication fork progression associated with an increased origin firing in mammals.

    “It has been reported that CHK1 inhibition slows replication fork progression associated with an increased origin firing in mammals [16, 17].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [16] Petermann, Woodcock, Helleday. Chk1 promotes replication fork progression by controlling replication initiation. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107:pp. 16090–16095. source
    • cites [17] Debatisse, 2016, Signaling from Mus81-Eme2-Dependent DNA Damage Elicited by Chk1 Deficiency Modulates Replication Fork Speed and Origin Usage, Cell Rep source

  • May combine two claims.

    Findingown data

    RPA32 is not phosphorylated in Spi1-overexpressing pre-leukemic cells or in cells with reduced Spi1 expression.

    “Consistent with the absence DNA breaks, RPA-32 protein, which is an activator and an early target of the primary CHK1 kinase ATR in the presence of single strand DNA regions [19, 20], was not phosphorylated in Spi1-overexpressing pre-leukemic cells, nor was it phosphorylated in cells with reduced Spi1 expression (treated with dox) (Figure 2A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    siRNA knockdown of ATR does not reduce CHK1 phosphorylation or modify the cell cycle.

    “Moreover, siRNA knockdown of ATR did not reduce CHK1 phosphorylation or modify the cell cycle.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Tautomycin induces a dose-dependent accumulation of inactive p-PP1α without affecting p-PP2A.

    “Tautomycin induced a dose-dependent accumulation of inactive p-PP1α without any effect on p-PP2A (Figure 3A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    CHK1 inhibition triggered a fast G1 phase arrest and cell death, which impeded successive analysis.

    “Unfortunately, our assay to define whether the lowest activity of CHK1 participates in accelerating fork elongation speed was unfruitful as CHK1 inhibition triggered a fast G1 phase arrest and cell death, which impeded successive analysis (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    CHK1 phosphorylation and erythroid differentiation are independent consequences of Spi1 silencing.

    “Importantly, we observed increased CHK1 phosphorylation in cells cultured in the presence of Epo, which allows erythroid differentiation (Figure 1A and 1C), or in the presence of SCF, which is not permissive for blast differentiation [13] (Figure 1B and 1C), indicating that CHK1 phosphorylation and erythroid differentiation are independent consequences of Spi1 silencing.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Guillouf, 2010, Spi1/PU.1 oncogene accelerates DNA replication fork elongation and promotes genetic instability in the absence of DNA breakage, Cancer research source

  • May combine two claims.

    Premisecitation

    Spi1 overexpression shortens S phase duration and increases replication fork speed in pre-leukemic cells.

    “We previously showed that constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads to pre-leukemic cells that have a shortened S phase duration with an increased replication fork speed and increased mutability in the absence of DNA breaks.”
    • Also stated in: § INTRODUCTION · plain
      “Moreover, Spi1 overexpression reduces S phase duration and increases genetic instability by accelerating the speed of replication forks [9].”
    • Also stated in: § PP1 activity accelerates fork progression speed and shortens S phase duration in Spi1 pre-leukemic cells · plain
      “As already published using this methodology [13], we found that Spi1 overexpression shortens S phase duration (Figure 4A, clone C2).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [9] Guillouf, 2007, Spi1/PU.1 participates in erythroleukemogenesis by inhibiting apoptosis in cooperation with Epo signaling and by blocking erythroid differentiation, Blood source
    • cites [13] Guillouf, 2010, Spi1/PU.1 oncogene accelerates DNA replication fork elongation and promotes genetic instability in the absence of DNA breakage, Cancer research source

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

    Premisecitation

    BCR-ABL disrupts ATR-dependent intra-S phase checkpoint in chronic myeloid leukemia after etoposide treatment, by causing DNA strand break formation.

    “The oncogenic BCR-ABL fusion protein disrupts ATR-dependent intra-S phase checkpoint in chronic myeloid leukemia after etoposide treatment, by causing DNA strand break formation [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Carroll, 2004, BCR/ABL translocates to the nucleus and disrupts an ATR-dependent intra-S phase checkpoint, Cancer Cell source

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

    Premisecitation

    CHK1 has been shown to be deregulated as a consequence of ATR kinase inhibition by oncogenes involved in hematopoietic malignancies.

    “CHK1 has been shown to be deregulated as a consequence of ATR kinase inhibition by oncogenes involved in hematopoietic malignancies.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    CHK1 prevents new origin firing by inhibiting CDK2 through CDC25A degradation, thus hindering the subsequent loading of CDC45 on chromatin to form the pre-initiation complex.

    “CHK1 prevents new origin firing by inhibiting CDK2 through CDC25A degradation, thus hindering the subsequent loading of CDC45 on chromatin to form the pre-initiation complex [34].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Bartek, 2004, Cell-cycle checkpoints and cancer, Nature source

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

    Premisecitation

    BCL-6 leads to reduced CHK1 phosphorylation through ATR inhibition, which subsequently facilitates DNA replication.

    “For instance, BCL-6, an oncogene involved in B lymphoma, leads to reduced CHK1 phosphorylation through ATR inhibition, which subsequently facilitates DNA replication [32].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Melnick, 2007, Bcl-6 mediates the germinal center B cell phenotype and lymphomagenesis through transcriptional repression of the DNA-damage sensor ATR, Nat Immunol source

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

    Premisenone given

    CHK1 plays an essential role in the regulation of DNA replication.

    “CHK1 plays an essential role in the regulation of DNA replication.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    In the presence of Spi1, PP1 maintains CHK1 in a low phosphorylation state and reduces S phase duration by accelerating fork progression.

    “In conclusion, our results demonstrate that in the presence of Spi1, PP1 maintains CHK1 in a low phosphorylation state and reduces S phase duration by accelerating fork progression.”
    • Also stated in: § Abstract · boosted
      “By exogenously modulating its activity, we demonstrate that PP1α is required to maintain CHK1 in a dephosphorylated state and, more importantly, that it is responsible for the accelerated replication fork progression in Spi1/PU.1-overexpressing cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    PP1 activity, but not PP2A activity, decreases CHK1 phosphorylation in pre-leukemic cells.

    “These findings suggest that PP1 activity, but not PP2A activity, decreases CHK1 phosphorylation in pre-leukemic cells.”
    • Also stated in: § Abstract · boosted
      “By exogenously modulating its activity, we demonstrate that PP1α is required to maintain CHK1 in a dephosphorylated state and, more importantly, that it is responsible for the accelerated replication fork progression in Spi1/PU.1-overexpressing cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Tautomycin specifically inhibits PP1 without affecting PP2A, and okadaic acid efficiently inhibits PP2A.

    “We determined the efficiency and specificity of these inhibitors by monitoring the level of Thr320 phosphorylation on the PP1 catalytic subunit α (p-PP1α) [24] and of Tyr307 phosphorylation on the PP2A catalytic subunit (p-PP2A) by immunoblotting with appropriate antibodies [25].”
    • Also stated in: § PP1α phosphatase reduces CHK1 phosphorylation in Spi1-overexpressing cells · plain
      “Tautomycin induced a dose-dependent accumulation of inactive p-PP1α without any effect on p-PP2A (Figure 3A).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [24] Dohadwala, da Cruz e Silva, Hall, Williams, Carbonaro-Hall, Nairn, Greengard, Berndt. Phosphorylation and inactivation of protein phosphatase 1 by cyclin-dependent kinases. Proceedings of the National Academy of Sciences of the United States of America. 1994; 91:pp. 6408–6412. source
    • cites [25] Hardwick, 2006, Effect of aspirin on the Wnt/beta-catenin pathway is mediated via protein phosphatase 2A, Oncogene source

  • May combine two claims.

    Premisecitation

    Spi1 alters replication by increasing fork progression speed without altering origin firing.

    “while Spi1 alters replication by increasing fork progression speed without altering origin firing.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Guillouf, 2010, Spi1/PU.1 oncogene accelerates DNA replication fork elongation and promotes genetic instability in the absence of DNA breakage, Cancer research source

  • May combine two claims.

    Interpretationreasoning

    Spi1 overexpression promotes cell transformation and contributes to leukemic progression by accelerating DNA replication, thus increasing the mutation load in pre-leukemic cells.

    “Thus, we proposed a model in which Spi1 overexpression promotes cell transformation and contributes to leukemic progression by accelerating DNA replication, thus increasing the mutation load in pre-leukemic cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    PP1 inhibition slows down the progression of Spi1 pre-leukemic cells towards S phase, while PP1α overexpression has the opposite effect.

    “In conclusion, PP1 inhibition slows down the progression of Spi1 pre-leukemic cells towards S phase, while PP1α overexpression has the opposite effect.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Both CldU and BrdU nucleotide analogues gave similar results in DNA fiber assays.

    “Of note, both nucleotide analogues, CldU and BrdU, gave similar results (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The effect of Spi1 on replication is mediated by the PP1 phosphatase that also regulates CHK1 kinase phosphorylation.

    “Here, we provide evidence that the effect of Spi1 on replication is mediated by the PP1 phosphatase that also regulates CHK1 kinase phosphorylation, which is a central mediator of the S phase checkpoint.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    CHK1 inhibitors abolish cytarabine resistance and reduce the speed of fork progression in response to cytarabine.

    “In that case, CHK1 inhibitors abolish cytarabine resistance and reduce the speed of fork progression in response to cytarabine [42].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Recher, 2016, CHK1 as a therapeutic target to bypass chemoresistance in AML, Sci Signal source

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

    Premisecitation

    High CHK1 expression in AML is a marker of poor prognosis and resistance to cytarabine treatment.

    “Recently, David and collaborators demonstrated that high CHK1 expression in AML is a marker of poor prognosis and resistance to cytarabine treatment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Recher, 2016, CHK1 as a therapeutic target to bypass chemoresistance in AML, Sci Signal source

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

    Study design and conductnone given

    Experiments were conducted with the ethical approval of Institut Gustave Roussy Area Standing Commitee on Animals.

    “Experiments were conducted with the ethical approval of Institut Gustave Roussy Area Standing Commitee on Animals.”
    Quote in the paperNot a substantial claim
26 of 26

  • The paper relies on this without support.

    Little is known about the determining events that favor the accumulation of mutations and the progression from the pre-leukemic to leukemic stage.

    “Although genomic alterations have been extensively characterized in AML [1], little is known about the determining events that favor the accumulation of mutations and the progression from the pre-leukemic to leukemic stage.”

  • The paper relies on this without support.

    The mechanism by which Spi1 induces a unique replicative stress remains elusive.

    “Interestingly, compared to other oncogenes or tumor suppressors, Spi1 induces a unique replicative stress, whose underlying mechanism remains elusive.”

  • The paper relies on this without support.

    CHK1 phosphorylation at Ser345 reflects CHK1 kinase activity.

    “our results showing that PP1α overexpression causes the acceleration of replication fork speed and reduces CHK1 phosphorylation, led us to examine the role of CHK1 in the replication phenotype observed in Spi1-overexpressing cells.”
3 of 3

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.

  • Conflicting stated cell concentrations

    Minor

    The methods state that 104 cells/mL were used, but later say that cells were diluted to 2 × 105 cells/mL for all experiments. These are different stated concentrations, and the latter claim includes the former experiment.

  • VE-822 is cited to the wrong Figure 2 panel

    Minor

    The text cites Figure 2B for the VE-822 experiment, but the figure caption assigns VE-822 treatment to Figure 2C. Figure 2B describes an ATR siRNA experiment instead.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Tavitian, 1996, Spi1/PU.1 transgenic mice develop multistep erythroleukemias, Mol Cell Biol, 16, 2453, 10.1128/mcb.16.5.2453 · DOI · Paper page

Cited by

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Related

Authors
Rimmelé, P., Esposito, M., Delestré, L., Guervilly, J.-H., Ridinger-Saison, M., Despras, E., Moreau-Gachelin, F., Rosselli, F., & Guillouf, C.
Affiliations
  • Inserm (FR)
  • Université Paris-Sud (FR)
  • Centre National de la Recherche Scientifique (FR)
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2017-03-14
Volume
8
Issue
23
Pages
37104-37114
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.16183
PMC
PMC5514894
OpenAlex
W2597828960
Semantic Scholar
de77c13dc29bd186d205fb1dbb19328f28de4556
Cited by
11
References
44
Citations by year
2026: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1
FWCI
0.30
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (Le Centre pour la Communication Scientifique Directe) (submittedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
PP1 phosphatase, Chk1, replication fork progression, DNA replication, replicative stress, leukemia, S-phase checkpoint, ATR kinase
MeSH terms
Checkpoint Kinase 1, Proto-Oncogene Protein Spi-1, Animals, Cell Cycle, Cells, Cultured, DNA Replication, Humans, Leukemia

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