Chk1

Summary

Gene Symbol: Chk1
Description: checkpoint kinase 1
Alias: CHK1, serine/threonine-protein kinase Chk1, CHK1 checkpoint homolog, Checkpoint, S. pombe, homolog of, 1, Chk1-S, cell cycle checkpoint kinase
Species: human
Products:     Chk1

Top Publications

  1. Carrassa L, Broggini M, Vikhanskaya F, Damia G. Characterization of the 5'flanking region of the human Chk1 gene: identification of E2F1 functional sites. Cell Cycle. 2003;2:604-9 pubmed
    b>Chk1 kinase is a key signal transducer in the checkpoint pathways responding to DNA damage. Chk1 has been shown to be transcriptionally down-regulated in response to cis-dichloro-diamino platinum treatment in a p53-dependent manner...
  2. Yarden R, Pardo Reoyo S, Sgagias M, Cowan K, Brody L. BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage. Nat Genet. 2002;30:285-9 pubmed
    ..Here we show that BRCA1 is essential for activating the Chk1 kinase that regulates DNA damage-induced G2/M arrest...
  3. Pouliot L, Chen Y, Bai J, Guha R, Martin S, Gottesman M, et al. Cisplatin sensitivity mediated by WEE1 and CHK1 is mediated by miR-155 and the miR-15 family. Cancer Res. 2012;72:5945-55 pubmed publisher
    ..Overexpression of the cell-cycle kinases WEE1 and CHK1 occurred commonly in cisplatin-resistant cells...
  4. Roshal M, Kim B, Zhu Y, Nghiem P, Planelles V. Activation of the ATR-mediated DNA damage response by the HIV-1 viral protein R. J Biol Chem. 2003;278:25879-86 pubmed
    ..As with DNA damage, activation of ATR by Vpr results in phosphorylation of Chk1. This study provides conclusive evidence of activation of the ATR-initiated DNA damage-signaling pathway by a viral ..
  5. Li G, Elder R, Qin K, Park H, Liang D, Zhao R. Phosphatase type 2A-dependent and -independent pathways for ATR phosphorylation of Chk1. J Biol Chem. 2007;282:7287-98 pubmed
    ..that, when activated by hydroxyurea, UV, or human immunodeficiency virus-1 Vpr, causes cell cycle arrest through Chk1-Ser(345) phosphorylation...
  6. Reinhardt H, Aslanian A, Lees J, Yaffe M. p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell. 2007;11:175-89 pubmed
    In response to DNA damage, eukaryotic cells activate ATM-Chk2 and/or ATR-Chk1 to arrest the cell cycle and initiate DNA repair...
  7. Lai M, Zimmerman E, Planelles V, Chen J. Activation of the ATR pathway by human immunodeficiency virus type 1 Vpr involves its direct binding to chromatin in vivo. J Virol. 2005;79:15443-51 pubmed
    ..of Vpr does not cause DNA double-strand breaks but rather induces ATR activation, as indicated by induction of Chk1 phosphorylation and the formation of gamma-H2AX and 53BP1 nuclear foci...
  8. Feijoo C, Hall Jackson C, Wu R, Jenkins D, Leitch J, Gilbert D, et al. Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing. J Cell Biol. 2001;154:913-23 pubmed
    ..Here we describe evidence for the participation of Chk1 in an intra-S phase checkpoint in mammalian cells...
  9. Demidova A, Aau M, Zhuang L, Yu Q. Dual regulation of Cdc25A by Chk1 and p53-ATF3 in DNA replication checkpoint control. J Biol Chem. 2009;284:4132-9 pubmed publisher
    ..A systematic screening of the protein kinase small interfering RNA library reveals that Chk1 and ataxia telangiectasia-mutated (ATM) and Rad3-related (ATR) are the main kinases responsible for intra-S-phase ..

More Information

Publications94

  1. Kastan M, Lim D. The many substrates and functions of ATM. Nat Rev Mol Cell Biol. 2000;1:179-86 pubmed
    ..Although it is hard to understand how a single gene product is involved in so many physiological processes, a clear picture is starting to emerge. ..
  2. Shieh S, Ahn J, Tamai K, Taya Y, Prives C. The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev. 2000;14:289-300 pubmed
    ..that a S20 kinase activity copurifies with the human homolog of the Schizosaccharomyces pombe checkpoint kinase, Chk1 (hCHK1)...
  3. Pabla N, Bhatt K, Dong Z. Checkpoint kinase 1 (Chk1)-short is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints. Proc Natl Acad Sci U S A. 2012;109:197-202 pubmed publisher
    Checkpoint kinase 1 (Chk1) is a key regulator of checkpoint signaling in both the unperturbed cell cycle and DNA damage response...
  4. Guervilly J, Macé Aimé G, Rosselli F. Loss of CHK1 function impedes DNA damage-induced FANCD2 monoubiquitination but normalizes the abnormal G2 arrest in Fanconi anemia. Hum Mol Genet. 2008;17:679-89 pubmed
    ..Moreover, we demonstrate that CHK1 and its interacting partner CLASPIN that act downstream in the ATR pathway are required for both FANCD2 ..
  5. Zhao B, Bower M, McDevitt P, Zhao H, Davis S, Johanson K, et al. Structural basis for Chk1 inhibition by UCN-01. J Biol Chem. 2002;277:46609-15 pubmed
    b>Chk1 is a serine-threonine kinase that plays an important role in the DNA damage response, including G(2)/M cell cycle control...
  6. Zhang Y, Otterness D, Chiang G, Xie W, Liu Y, Mercurio F, et al. Genotoxic stress targets human Chk1 for degradation by the ubiquitin-proteasome pathway. Mol Cell. 2005;19:607-18 pubmed
    The Chk1 kinase is a major effector of S phase checkpoint signaling during the cellular response to genotoxic stress. Here, we report that replicative stress induces the polyubiquitination and degradation of Chk1 in human cells...
  7. Gagou M, Zuazua Villar P, Meuth M. Enhanced H2AX phosphorylation, DNA replication fork arrest, and cell death in the absence of Chk1. Mol Biol Cell. 2010;21:739-52 pubmed publisher
    ..enhanced in response to replication inhibitors but not ionizing radiation in HCT116 or SW480 cells depleted of Chk1. Although H2AX phosphorylation precedes the induction of apoptosis in such cells, our results suggest that cells ..
  8. Liu Q, Guntuku S, Cui X, Matsuoka S, Cortez D, Tamai K, et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 2000;14:1448-59 pubmed
    b>Chk1, an evolutionarily conserved protein kinase, has been implicated in cell cycle checkpoint control in lower eukaryotes...
  9. Lin J, Dutta A. ATR pathway is the primary pathway for activating G2/M checkpoint induction after re-replication. J Biol Chem. 2007;282:30357-62 pubmed
    ..ATM kinase and the Mre11-Rad50-Nbs1 complex do not appear to play significant roles in the checkpoint. Chk1 activation occurs at early stages, whereas Chk2 activation occurs much later...
  10. Tonic I, Yu W, Park Y, Chen C, Hay N. Akt activation emulates Chk1 inhibition and Bcl2 overexpression and abrogates G2 cell cycle checkpoint by inhibiting BRCA1 foci. J Biol Chem. 2010;285:23790-8 pubmed publisher
    ..Here we show that the activation of Akt is sufficient to promote these two principal processes, by inhibiting Chk1 activation with concomitant inhibition of apoptosis...
  11. Niida H, Tsuge S, Katsuno Y, Konishi A, Takeda N, Nakanishi M. Depletion of Chk1 leads to premature activation of Cdc2-cyclin B and mitotic catastrophe. J Biol Chem. 2005;280:39246-52 pubmed
    ..We demonstrate here the essential role of the ATM/ATR-p53 pathway in mitotic catastrophe from premature mitosis. Chk1 deficiency resulted in a premature onset of mitosis because of abnormal activation of cyclin B-Cdc2 and led to the ..
  12. Rodriguez R, Gagou M, Meuth M. Apoptosis induced by replication inhibitors in Chk1-depleted cells is dependent upon the helicase cofactor Cdc45. Cell Death Differ. 2008;15:889-98 pubmed publisher
    Checkpoint kinase 1 (Chk1) responds to disruption of DNA replication to maintain the integrity of stalled forks, promote homologous recombination-mediated repair of replication fork lesions, and control inappropriate firing of replication ..
  13. Maya Mendoza A, Petermann E, Gillespie D, Caldecott K, Jackson D. Chk1 regulates the density of active replication origins during the vertebrate S phase. EMBO J. 2007;26:2719-31 pubmed
    The checkpoint kinase 1 (Chk1) preserves genome integrity when replication is performed on damaged templates. Recently, Chk1 has also been implicated in regulating different aspects of unperturbed S phase...
  14. Goto H, Izawa I, Li P, Inagaki M. Novel regulation of checkpoint kinase 1: Is checkpoint kinase 1 a good candidate for anti-cancer therapy?. Cancer Sci. 2012;103:1195-200 pubmed publisher
    ..to genetic defect(s) in the ATM (ataxia-telangiectasia mutated)-Chk2-p53 pathway, an ATR (ATM- and Rad3-related)-Chk1-Cdc25 route is the sole checkpoint pathway in a majority of cancer cells...
  15. Huang M, Miao Z, Zhu H, Cai Y, Lu W, Ding J. Chk1 and Chk2 are differentially involved in homologous recombination repair and cell cycle arrest in response to DNA double-strand breaks induced by camptothecins. Mol Cancer Ther. 2008;7:1440-9 pubmed publisher
    ..In this process, both checkpoint kinases 1 and 2 (Chk1 and Chk2, respectively) are activated, but their differential roles, especially in the coordination of checkpoint ..
  16. Shimada M, Niida H, Zineldeen D, Tagami H, Tanaka M, Saito H, et al. Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression. Cell. 2008;132:221-32 pubmed publisher
    ..H3-T11 phosphorylation occurs throughout the cell cycle and is Chk1 dependent in vivo...
  17. Verlinden L, Vanden Bempt I, Eelen G, Drijkoningen M, Verlinden I, Marchal K, et al. The E2F-regulated gene Chk1 is highly expressed in triple-negative estrogen receptor /progesterone receptor /HER-2 breast carcinomas. Cancer Res. 2007;67:6574-81 pubmed
    We previously showed that checkpoint kinase 1 (Chk1) and Claspin, two DNA-damage checkpoint proteins, were down-regulated by 1,25-dihydroxyvitamin D(3), a known inhibitor of cell proliferation...
  18. Sengupta S, Robles A, Linke S, Sinogeeva N, Zhang R, Pedeux R, et al. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J Cell Biol. 2004;166:801-13 pubmed
    ..The active Chk1 kinase was essential for both the accurate focal colocalization of 53BP1 with BLM and the consequent stabilization ..
  19. Rodriguez R, Meuth M. Chk1 and p21 cooperate to prevent apoptosis during DNA replication fork stress. Mol Biol Cell. 2006;17:402-12 pubmed
    ..potent inducers of death in S-phase cells upon small interfering RNA-mediated depletion of the checkpoint kinase Chk1. This death response is independent of p53 and Chk2...
  20. Inoue Y, Kitagawa M, Taya Y. Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage. EMBO J. 2007;26:2083-93 pubmed
    ..However, the phosphorylation of pRB at Ser612 was conducted by Chk1/2 after DNA damage, and inhibition of ATM-Chk1/2 activity suppressed the phosphorylation of Ser612 and the binding ..
  21. Adamson A, Beardsley D, Kim W, Gao Y, Baskaran R, Brown K. Methylator-induced, mismatch repair-dependent G2 arrest is activated through Chk1 and Chk2. Mol Biol Cell. 2005;16:1513-26 pubmed
    ..Here, we show that MNNG exposure results in activation of the cell cycle checkpoint kinases ATM, Chk1, and Chk2, each of which has been implicated in the triggering of the G2/M checkpoint response...
  22. Herman Antosiewicz A, Singh S. Checkpoint kinase 1 regulates diallyl trisulfide-induced mitotic arrest in human prostate cancer cells. J Biol Chem. 2005;280:28519-28 pubmed
    ..In conclusion, the results of the present study suggest existence of a checkpoint kinase 1-dependent mechanism for diallyl trisulfide-induced mitotic arrest in human prostate cancer cells. ..
  23. Bourke E, Brown J, Takeda S, Hochegger H, Morrison C. DNA damage induces Chk1-dependent threonine-160 phosphorylation and activation of Cdk2. Oncogene. 2010;29:616-24 pubmed publisher
    ..Cdk2 controls normal centrosome duplication, but Chk1-dependent centrosome amplification also occurs after DNA damage...
  24. Liu S, Bekker Jensen S, Mailand N, Lukas C, Bartek J, Lukas J. Claspin operates downstream of TopBP1 to direct ATR signaling towards Chk1 activation. Mol Cell Biol. 2006;26:6056-64 pubmed
    TopBP1 and Claspin are adaptor proteins that facilitate phosphorylation of Chk1 by the ATR kinase in response to genotoxic stress...
  25. Sanchez Y, Wong C, Thoma R, Richman R, Wu Z, Piwnica Worms H, et al. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science. 1997;277:1497-501 pubmed
    ..A human gene was identified that encodes the protein Chk1, a homolog of the Schizosaccharomyces pombe Chk1 protein kinase, which is required for the DNA damage checkpoint...
  26. Graves P, Yu L, Schwarz J, Gales J, Sausville E, O Connor P, et al. The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01. J Biol Chem. 2000;275:5600-5 pubmed
    ..The checkpoint kinases, Chk1 and Cds1, are proposed to regulate the interactions between human Cdc25C and 14-3-3 proteins by phosphorylating ..
  27. Qing P, Han L, Bin L, Yan L, Ping W. USP7 regulates the stability and function of HLTF through deubiquitination. J Cell Biochem. 2011;112:3856-62 pubmed publisher
    ..Thus, our results delineate a previously unknown USP7-HLTF-PCNA molecular network controlling DNA damage response. ..
  28. Sinha S, Singh R, Bhattacharya N, Mukherjee N, Ghosh S, Alam N, et al. Frequent alterations of LOH11CR2A, PIG8 and CHEK1 genes at chromosomal 11q24.1-24.2 region in breast carcinoma: clinical and prognostic implications. Mol Oncol. 2011;5:454-64 pubmed publisher
    ..Thus, our study suggests that LOH11CR2A, PIG8 and CHEK1 are candidate tumor suppressor genes associated with breast carcinoma and have significant clinical as well as prognostic importance. ..
  29. Matsuyama M, Goto H, Kasahara K, Kawakami Y, Nakanishi M, Kiyono T, et al. Nuclear Chk1 prevents premature mitotic entry. J Cell Sci. 2011;124:2113-9 pubmed publisher
    b>Chk1 inhibits the premature activation of the cyclin-B1-Cdk1. However, it remains controversial whether Chk1 inhibits Cdk1 in the centrosome or in the nucleus before the G2-M transition...
  30. Scorah J, McGowan C. Claspin and Chk1 regulate replication fork stability by different mechanisms. Cell Cycle. 2009;8:1036-43 pubmed
    The checkpoint mediator protein Claspin facilitates the phosphorylation and activation of Chk1 by ATR and thus is required for efficient DNA replication...
  31. Ikegami Y, Goto H, Kiyono T, Enomoto M, Kasahara K, Tomono Y, et al. Chk1 phosphorylation at Ser286 and Ser301 occurs with both stalled DNA replication and damage checkpoint stimulation. Biochem Biophys Res Commun. 2008;377:1227-31 pubmed publisher
    We previously reported Chk1 to be phosphorylated at Ser286 and Ser301 by cyclin-dependent kinase (Cdk) 1 during mitosis [T. Shiromizu et al., Genes Cells 11 (2006) 477-485]...
  32. Ellison V, Stillman B. Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA. PLoS Biol. 2003;1:E33 pubmed
  33. Pooley K, Baynes C, Driver K, Tyrer J, Azzato E, Pharoah P, et al. Common single-nucleotide polymorphisms in DNA double-strand break repair genes and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17:3482-9 pubmed publisher
    ..20; 95% CI, 1.07-1.36; P trend = 0.002). In summary, there was little evidence of breast cancer susceptibility with any of the SNPs studied, but larger studies would be needed to confirm subgroup effects. ..
  34. Kasahara K, Goto H, Enomoto M, Tomono Y, Kiyono T, Inagaki M. 14-3-3gamma mediates Cdc25A proteolysis to block premature mitotic entry after DNA damage. EMBO J. 2010;29:2802-12 pubmed publisher
    ..of 14-3-3 (beta and zeta isoforms in mammalian cells and Rad24 in fission yeast) bind to Ser345-phosphorylated Chk1 and promote its nuclear retention...
  35. Matsuura K, Wakasugi M, Yamashita K, Matsunaga T. Cleavage-mediated activation of Chk1 during apoptosis. J Biol Chem. 2008;283:25485-91 pubmed publisher
    The Chk1 kinase is highly conserved from yeast to humans and is well known to function in the cell cycle checkpoint induced by genotoxic or replication stress...
  36. Zhang W, Poh A, Fanous A, Eastman A. DNA damage-induced S phase arrest in human breast cancer depends on Chk1, but G2 arrest can occur independently of Chk1, Chk2 or MAPKAPK2. Cell Cycle. 2008;7:1668-77 pubmed
    Checkpoint kinases Chk1 and Chk2 are two key components in the DNA damage-activated checkpoint signaling pathways...
  37. Wang X, Li J, Feng X, Wang Q, Guan D, Shen Z. Involvement of the role of Chk1 in lithium-induced G2/M phase cell cycle arrest in hepatocellular carcinoma cells. J Cell Biochem. 2008;104:1181-91 pubmed publisher
    ..Checkpoint kinase 1 (Chk1), a critical enzyme in DNA damage-induced G2/M arrest, was at least partially responsible for the lithium action...
  38. Smith J, Tho L, Xu N, Gillespie D. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res. 2010;108:73-112 pubmed publisher
    ..responses to DNA damage are coordinated primarily by two distinct kinase signaling cascades, the ATM-Chk2 and ATR-Chk1 pathways, which are activated by DNA double-strand breaks (DSBs) and single-stranded DNA respectively...
  39. Mazumder Indra D, Mitra S, Singh R, Dutta S, Roy A, Mondal R, et al. Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: clinical and prognostic implications. Int J Cancer. 2011;129:1859-71 pubmed publisher
    ..Thus, our data suggest that inactivation of EI24 and CHEK1 through two independent mechanisms contributes to the development of CACX. ..
  40. Brazelle W, Kreahling J, Gemmer J, Ma Y, Cress W, Haura E, et al. Histone deacetylase inhibitors downregulate checkpoint kinase 1 expression to induce cell death in non-small cell lung cancer cells. PLoS ONE. 2010;5:e14335 pubmed publisher
    ..Here, we show that protein levels of checkpoint kinase 1 (Chk1), which has a major role in G(2) cell cycle checkpoint regulation, was markedly reduced at the protein and ..
  41. Dai Y, Grant S. New insights into checkpoint kinase 1 in the DNA damage response signaling network. Clin Cancer Res. 2010;16:376-83 pubmed publisher
    ..This has prompted the development of agents targeting DDR signaling pathways, particularly checkpoint kinase 1 (Chk1), which contributes to all currently defined cell cycle checkpoints, including G1/S, intra-S-phase, G2/M, and the ..
  42. Peng C, Graves P, Thoma R, Wu Z, Shaw A, Piwnica Worms H. Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science. 1997;277:1501-5 pubmed
    ..b>Chk1, a fission yeast kinase involved in the DNA damage checkpoint response, phosphorylated Cdc25C in vitro on serine-..
  43. Petsalaki E, Akoumianaki T, Black E, Gillespie D, Zachos G. Phosphorylation at serine 331 is required for Aurora B activation. J Cell Biol. 2011;195:449-66 pubmed publisher
    ..b>Chk1 kinase is essential for Ser331 phosphorylation during unperturbed prometaphase or during spindle disruption by ..
  44. Enomoto M, Goto H, Tomono Y, Kasahara K, Tsujimura K, Kiyono T, et al. Novel positive feedback loop between Cdk1 and Chk1 in the nucleus during G2/M transition. J Biol Chem. 2009;284:34223-30 pubmed publisher
    b>Chk1, one of the critical transducers in DNA damage/replication checkpoints, prevents entry into mitosis through inhibition of Cdk1 activity. However, it has remained unclear how this inhibition is cancelled at the G(2)/M transition...
  45. Taricani L, Shanahan F, Parry D. Replication stress activates DNA polymerase alpha-associated Chk1. Cell Cycle. 2009;8:482-9 pubmed
    b>Chk1 contributes to both intra-S and DNA damage checkpoint responses...
  46. Xiao Z, Chen Z, Gunasekera A, Sowin T, Rosenberg S, Fesik S, et al. Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. J Biol Chem. 2003;278:21767-73 pubmed
    ..and Lukas J. (2001) Nature 410, 842-847). The degradation of Cdc25A is abrogated by caffeine, which implicates Chk1 as the potential mediator (Mailand, N., Falck, J., Lukas, C., Syljuasen, R. G., Welcker, M., Bartek, J...
  47. Puc J, Keniry M, Li H, Pandita T, Choudhury A, Memeo L, et al. Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell. 2005;7:193-204 pubmed
    ..The checkpoint defect was traced to the ability of AKT to phosphorylate CHK1 at serine 280, since a nonphosphorylated mutant of CHK1 (S280A) complemented the checkpoint defect and restored ..
  48. Krämer A, Mailand N, Lukas C, Syljuåsen R, Wilkinson C, Nigg E, et al. Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase. Nat Cell Biol. 2004;6:884-91 pubmed
    ..Here, we show that human Chk1 kinase localizes to interphase, but not mitotic, centrosomes...
  49. Wang Y, Qin J. MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation. Proc Natl Acad Sci U S A. 2003;100:15387-92 pubmed
    ..with the ATR (ATM- and Rad3-related) kinase to form a signaling module and regulate the phosphorylation of Chk1 and SMC1 (structure maintenance of chromosome 1)...
  50. Petermann E, Maya Mendoza A, Zachos G, Gillespie D, Jackson D, Caldecott K. Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase. Mol Cell Biol. 2006;26:3319-26 pubmed
    b>Chk1 protein kinase maintains replication fork stability in metazoan cells in response to DNA damage and DNA replication inhibitors...
  51. Shiromizu T, Goto H, Tomono Y, Bartek J, Totsukawa G, Inoko A, et al. Regulation of mitotic function of Chk1 through phosphorylation at novel sites by cyclin-dependent kinase 1 (Cdk1). Genes Cells. 2006;11:477-85 pubmed
    b>Chk1 is phosphorylated at Ser317 and Ser345 by ATR in response to stalled replication and genotoxic stresses. This Chk1 activation is thought to play critical roles in the prevention of premature mitosis...
  52. Tang J, Erikson R, Liu X. Checkpoint kinase 1 (Chk1) is required for mitotic progression through negative regulation of polo-like kinase 1 (Plk1). Proc Natl Acad Sci U S A. 2006;103:11964-9 pubmed
    Although the essential function of checkpoint kinase 1 (Chk1) in DNA damage response has been well established, the role of Chk1 in normal cell cycle progression is unclear...
  53. Chini C, Chen J. Repeated phosphopeptide motifs in human Claspin are phosphorylated by Chk1 and mediate Claspin function. J Biol Chem. 2006;281:33276-82 pubmed
    Claspin is a checkpoint protein involved in ATR (ataxia telangiectasia mutated- and Rad3-related)-dependent Chk1 activation in Xenopus and human cells...
  54. Sørensen C, Syljuåsen R, Falck J, Schroeder T, Ronnstrand L, Khanna K, et al. Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. Cancer Cell. 2003;3:247-58 pubmed
    b>Chk1 kinase coordinates cell cycle progression and preserves genome integrity...
  55. Gatei M, Sloper K, Sorensen C, Syljuasen R, Falck J, Hobson K, et al. Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation. J Biol Chem. 2003;278:14806-11 pubmed
    ..The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2...
  56. Shtivelman E, Sussman J, Stokoe D. A role for PI 3-kinase and PKB activity in the G2/M phase of the cell cycle. Curr Biol. 2002;12:919-24 pubmed
    ..Inhibition of PI 3-kinase results in activation of Chk1, whereas caPKB inhibits the ability of Chk1 to become activated in response to treatment with hydroxyurea...
  57. Zhao H, Piwnica Worms H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol Cell Biol. 2001;21:4129-39 pubmed
    b>Chk1 is an evolutionarily conserved protein kinase that regulates cell cycle progression in response to checkpoint activation...
  58. Zhang Y, Brognard J, Coughlin C, You Z, Dolled Filhart M, Aslanian A, et al. The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress. Mol Cell. 2009;35:442-53 pubmed publisher
    ATR and Chk1 are two key protein kinases in the replication checkpoint. Activation of ATR-Chk1 has been extensively investigated, but checkpoint termination and replication fork restart are less well understood...
  59. Jiang K, Pereira E, Maxfield M, Russell B, Goudelock D, Sanchez Y. Regulation of Chk1 includes chromatin association and 14-3-3 binding following phosphorylation on Ser-345. J Biol Chem. 2003;278:25207-17 pubmed
    ..The conserved checkpoint kinase Chk1 regulates mitotic progression in response to DNA damage and replication interference by blocking the activation of ..
  60. Zhao H, Watkins J, Piwnica Worms H. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci U S A. 2002;99:14795-800 pubmed
    ..In mice, Chk1 provides an essential function in the absence of environmentally imposed genotoxic stress...
  61. Goudelock D, Jiang K, Pereira E, Russell B, Sanchez Y. Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex. J Biol Chem. 2003;278:29940-7 pubmed
    ..The conserved checkpoint kinase, Chk1, regulates mitotic progression in response to DNA damage by blocking the activation of Cdk1/cyclin B...
  62. Hromas R, Williamson E, Fnu S, Lee Y, Park S, Beck B, et al. Chk1 phosphorylation of Metnase enhances DNA repair but inhibits replication fork restart. Oncogene. 2012;31:4245-54 pubmed publisher
    b>Chk1 both arrests replication forks and enhances repair of DNA damage by phosphorylating downstream effectors...
  63. Cho S, Toouli C, Fujii G, Crain C, Parry D. Chk1 is essential for tumor cell viability following activation of the replication checkpoint. Cell Cycle. 2005;4:131-9 pubmed
    b>Chk1 (checkpoint kinase 1) is an evolutionarily conserved serine/threonine kinase involved in DNA damage responses...
  64. Cavelier C, Didier C, Prade N, Mansat De Mas V, Manenti S, Recher C, et al. Constitutive activation of the DNA damage signaling pathway in acute myeloid leukemia with complex karyotype: potential importance for checkpoint targeting therapy. Cancer Res. 2009;69:8652-61 pubmed publisher
    ..We show that antagonizing CHK1 kinase with a small inhibitory compound or by RNA interference strongly reduces the clonogenic properties of high-..
  65. Sørensen C, Hansen L, Dziegielewski J, Syljuåsen R, Lundin C, Bartek J, et al. The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol. 2005;7:195-201 pubmed
    The essential checkpoint kinase Chk1 is required for cell-cycle delays after DNA damage or blocked DNA replication. However, it is unclear whether Chk1 is involved in the repair of damaged DNA...
  66. Chen P, Luo C, Deng Y, Ryan K, Register J, Margosiak S, et al. The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: implications for Chk1 regulation. Cell. 2000;100:681-92 pubmed
    The checkpoint kinase Chk1 is an important mediator of cell cycle arrest following DNA damage. The 1...
  67. Wilsker D, Petermann E, Helleday T, Bunz F. Essential function of Chk1 can be uncoupled from DNA damage checkpoint and replication control. Proc Natl Acad Sci U S A. 2008;105:20752-7 pubmed publisher
    b>Chk1 is widely known as a DNA damage checkpoint signaling protein. Unlike many other checkpoint proteins, Chk1 also plays an essential but poorly defined role in the proliferation of unperturbed cells...
  68. Kreutzer J, Guerra B. The regulatory beta-subunit of protein kinase CK2 accelerates the degradation of CDC25A phosphatase through the checkpoint kinase Chk1. Int J Oncol. 2007;31:1251-9 pubmed
    ..b>Chk1 has been shown to phosphorylate CDC25 family members down-regulating their phosphatase activity through distinct ..
  69. Wang X, Kennedy R, Ray K, Stuckert P, Ellenberger T, D Andrea A. Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway. Mol Cell Biol. 2007;27:3098-108 pubmed
    ..Here, we show that, in response to DNA damage, Chk1 directly phosphorylates the FANCE subunit of the FA core complex on two conserved sites (threonine 346 and serine ..
  70. Zachos G, Black E, Walker M, Scott M, Vagnarelli P, Earnshaw W, et al. Chk1 is required for spindle checkpoint function. Dev Cell. 2007;12:247-60 pubmed
    The spindle checkpoint delays anaphase onset in cells with mitotic spindle defects. Here, we show that Chk1, a component of the DNA damage and replication checkpoints, protects vertebrate cells against spontaneous chromosome ..
  71. Schmitt E, Boutros R, Froment C, Monsarrat B, Ducommun B, Dozier C. CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage. J Cell Sci. 2006;119:4269-75 pubmed
    ..Centrosome-associated checkpoint kinase 1 (CHK1) has been proposed to contribute to the proper timing of a normal cell division cycle by inhibiting the activation ..
  72. Enders G. Expanded roles for Chk1 in genome maintenance. J Biol Chem. 2008;283:17749-52 pubmed publisher
    b>Chk1 is a conserved kinase that imposes cell cycle delays in response to impediments to DNA replication...
  73. Alderton G, Galbiati L, Griffith E, Surinya K, Neitzel H, Jackson A, et al. Regulation of mitotic entry by microcephalin and its overlap with ATR signalling. Nat Cell Biol. 2006;8:725-33 pubmed
    ..MCPH1 have implicated the protein it encodes as a DNA-damage response protein that regulates the transcription of Chk1 and BRCA1, two genes involved in the response to DNA damage...
  74. Durkin S, Arlt M, Howlett N, Glover T. Depletion of CHK1, but not CHK2, induces chromosomal instability and breaks at common fragile sites. Oncogene. 2006;25:4381-8 pubmed
    ..fragile site stability, we have investigated the effects of depletion of the cell cycle checkpoint kinases, CHK1 and CHK2 on common fragile site stability in human cells...
  75. Choi J, Lindsey Boltz L, Sancar A. Reconstitution of a human ATR-mediated checkpoint response to damaged DNA. Proc Natl Acad Sci U S A. 2007;104:13301-6 pubmed
    ..ATR in the presence of topoisomerase II binding protein 1 (TopBP1) mediator/adaptor protein phosphorylates the Chk1 signal-transducing kinase in a reaction that is strongly dependent on the presence of DNA containing bulky base ..
  76. Myers K, Gagou M, Zuazua Villar P, Rodriguez R, Meuth M. ATR and Chk1 suppress a caspase-3-dependent apoptotic response following DNA replication stress. PLoS Genet. 2009;5:e1000324 pubmed publisher
    ..Much less is known about the control of apoptosis following DNA replication stress. Recent work indicates that Chk1, the downstream phosphorylation target of ATR, protects cells from apoptosis induced by DNA replication inhibitors ..
  77. Syljuåsen R, Sørensen C, Hansen L, Fugger K, Lundin C, Johansson F, et al. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Mol Cell Biol. 2005;25:3553-62 pubmed
    Human checkpoint kinase 1 (Chk1) is an essential kinase required to preserve genome stability...
  78. Beckerman R, Donner A, Mattia M, Peart M, Manley J, Espinosa J, et al. A role for Chk1 in blocking transcriptional elongation of p21 RNA during the S-phase checkpoint. Genes Dev. 2009;23:1364-77 pubmed publisher
    ..Here we show that ablation of the protein kinase Chk1 rescues the p21 transcription elongation defect when cells are blocked in S phase, as measured by increases in both ..
  79. Chini C, Chen J. Human claspin is required for replication checkpoint control. J Biol Chem. 2003;278:30057-62 pubmed
    Claspin is a newly identified protein that regulates Chk1 activation in Xenopus. In the present study we investigated the role of human Claspin in the DNA damage/replication checkpoint in mammalian cells...
  80. Petermann E, Woodcock M, Helleday T. Chk1 promotes replication fork progression by controlling replication initiation. Proc Natl Acad Sci U S A. 2010;107:16090-5 pubmed publisher
    ..Origin activation is controlled by the ATR checkpoint kinase and its downstream effector kinase Chk1, which suppresses origin firing in response to replication blocks and during normal S phase by inhibiting the ..
  81. Chen M, Ryan C, Piwnica Worms H. Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding. Mol Cell Biol. 2003;23:7488-97 pubmed
    The order and fidelity of cell cycle events in mammals is intimately linked to the integrity of the Chk1 kinase-Cdc25A phosphatase pathway...
  82. Yang X, Shiotani B, Classon M, Zou L. Chk1 and Claspin potentiate PCNA ubiquitination. Genes Dev. 2008;22:1147-52 pubmed publisher
    b>Chk1 is a kinase crucial for genomic integrity and an effector of ATR (ATM and Rad3-related) in DNA damage response...
  83. Leung Pineda V, Ryan C, Piwnica Worms H. Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit. Mol Cell Biol. 2006;26:7529-38 pubmed
    In higher eukaryotic organisms, the checkpoint kinase 1 (Chk1) contributes essential functions to both cell cycle and checkpoint control...
  84. Ball H, Myers J, Cortez D. ATRIP binding to replication protein A-single-stranded DNA promotes ATR-ATRIP localization but is dispensable for Chk1 phosphorylation. Mol Biol Cell. 2005;16:2372-81 pubmed
    ..the ATRIP-RPA-ssDNA interaction is not absolutely essential for ATR activation because ATR phosphorylates Chk1 in cells expressing only a mutant of ATRIP that does not bind to RPA-ssDNA...
  85. Leung Pineda V, Huh J, Piwnica Worms H. DDB1 targets Chk1 to the Cul4 E3 ligase complex in normal cycling cells and in cells experiencing replication stress. Cancer Res. 2009;69:2630-7 pubmed publisher
    The Chk1 protein kinase preserves genome integrity in normal proliferating cells and in cells experiencing replicative and genotoxic stress. Chk1 is currently being targeted in anticancer regimens...