CHK1

Summary

Gene Symbol: CHK1
Description: serine/threonine protein kinase CHK1
Alias: serine/threonine protein kinase CHK1
Species: Saccharomyces cerevisiae S288c
Products:     CHK1

Top Publications

  1. Myung K, Datta A, Kolodner R. Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae. Cell. 2001;104:397-408 pubmed
    ..Mutations in Saccharomyces cerevisiae RFC5, DPB11, MEC1, DDC2 MEC3, RAD53, CHK1, PDS1, and DUN1 increased the rate of genome rearrangements up to 200-fold whereas mutations in RAD9, RAD17, RAD24, ..
  2. Wood M, Sanchez Y. Deregulated Ras signaling compromises DNA damage checkpoint recovery in S. cerevisiae. Cell Cycle. 2010;9:3353-63 pubmed publisher
    ..The ira1? ira2? recovery defect requires the checkpoint kinase Chk1 and the cAMP-dependent protein kinase (PKA) catalytic subunit Tpk2...
  3. Searle J, Schollaert K, Wilkins B, Sanchez Y. The DNA damage checkpoint and PKA pathways converge on APC substrates and Cdc20 to regulate mitotic progression. Nat Cell Biol. 2004;6:138-45 pubmed
    The conserved checkpoint kinases Chk1 and Rad53-Dun1 block the metaphase to anaphase transition by the phosphorylation and stabilization of securin, and block the mitotic exit network regulated by the Bfa1-Bub2 complex...
  4. Sanchez Y, Bachant J, Wang H, Hu F, Liu D, Tetzlaff M, et al. Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science. 1999;286:1166-71 pubmed
    ..yeast and mammals, mitotic arrest in response to DNA damage requires inhibitory Cdk phosphorylation regulated by Chk1. This study indicates that Chk1 is required for function of the DNA damage checkpoint in Saccharomyces cerevisiae ..
  5. Wang H, Liu D, Wang Y, Qin J, Elledge S. Pds1 phosphorylation in response to DNA damage is essential for its DNA damage checkpoint function. Genes Dev. 2001;15:1361-72 pubmed
    ..Phosphorylation of Pds1 is Mec1 and Chk1 dependent in vivo...
  6. Maringele L, Lydall D. EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants. Genes Dev. 2002;16:1919-33 pubmed
    We have examined the role of checkpoint pathways in responding to a yku70Delta defect in budding yeast. We show that CHK1, MEC1, and RAD9 checkpoint genes are required for efficient cell cycle arrest of yku70Delta mutants cultured at 37 ..
  7. Blankley R, Lydall D. A domain of Rad9 specifically required for activation of Chk1 in budding yeast. J Cell Sci. 2004;117:601-8 pubmed
    ..the activity of the Mec1 kinase to the activation of two parallel signalling pathways dependent on the Rad53 and Chk1 kinases. The mechanisms by which Rad9 interacts with, and activates, Rad53 are well understood...
  8. Chen Y, Caldwell J, Pereira E, Baker R, Sanchez Y. ATRMec1 phosphorylation-independent activation of Chk1 in vivo. J Biol Chem. 2009;284:182-90 pubmed publisher
    The conserved protein kinase Chk1 is a player in the defense against DNA damage and replication blocks. The current model is that after DNA damage or replication blocks, ATR(Mec1) phosphorylates Chk1 on the non-catalytic C-terminal domain...
  9. Kaochar S, Shanks L, Weinert T. Checkpoint genes and Exo1 regulate nearby inverted repeat fusions that form dicentric chromosomes in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2010;107:21605-10 pubmed publisher
    ..pathway, whereas in a second pathway the ATR-like kinases Mec1 and Tel1, adaptor protein Rad9, and effector kinases Chk1 and Dun1 act independently of Exo1 to prevent inverted repeat fusion...

More Information

Publications39

  1. Schollaert K, Poisson J, Searle J, Schwanekamp J, Tomlinson C, Sanchez Y. A role for Saccharomyces cerevisiae Chk1p in the response to replication blocks. Mol Biol Cell. 2004;15:4051-63 pubmed
    ..cerevisiae and suggest that at least in some genetic backgrounds, the Chk1p/securin pathway is required for the recovery from stalled or collapsed replication forks. ..
  2. Woolstencroft R, Beilharz T, Cook M, Preiss T, Durocher D, Tyers M. Ccr4 contributes to tolerance of replication stress through control of CRT1 mRNA poly(A) tail length. J Cell Sci. 2006;119:5178-92 pubmed
    ..Moreover, because ccr4Delta and chk1Delta exhibited epistasis in several genetic contexts, we infer that Ccr4 and Chk1 act in the same pathway to overcome replication stress...
  3. Koepp D, Kile A, Swaminathan S, Rodriguez Rivera V. The F-box protein Dia2 regulates DNA replication. Mol Biol Cell. 2006;17:1540-8 pubmed
    ..Interestingly, prolonging G1-phase in dia2 cells prevents the accumulation of DNA damage in S-phase. We propose that Dia2 is an origin-binding protein that plays a role in regulating DNA replication. ..
  4. Segurado M, Diffley J. Separate roles for the DNA damage checkpoint protein kinases in stabilizing DNA replication forks. Genes Dev. 2008;22:1816-27 pubmed publisher
    ..Finally, our analysis indicates that a second downstream effector kinase, Chk1, can stabilize replication forks in the absence of Rad53...
  5. Bracesco N, Candreva E, Keszenman D, Sánchez A, Soria S, Dell M, et al. Roles of Saccharomyces cerevisiae RAD17 and CHK1 checkpoint genes in the repair of double-strand breaks in cycling cells. Radiat Environ Biophys. 2007;46:401-7 pubmed
    ..We analysed the putative dual functions of Rad17 and Chk1 as checkpoints and in DNA repair using mutant strains of Saccharomyces cerevisiae...
  6. Tsolou A, Lydall D. Mrc1 protects uncapped budding yeast telomeres from exonuclease EXO1. DNA Repair (Amst). 2007;6:1607-17 pubmed
    ..Our observations show that Mrc1, a core component of the replication fork, plays an important role in telomere capping, protecting from nucleases and checkpoint pathways. ..
  7. Searle J, Wood M, Kaur M, Tobin D, Sanchez Y. Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage. PLoS Genet. 2011;7:e1002176 pubmed publisher
    ..The sensor-associated kinase, Mec1, phosphorylates two downstream kinases, Chk1 and Rad53. Activation of Chk1 and Rad53 prevents anaphase and causes inhibition of the mitotic exit network...
  8. Covo S, Chiou E, Gordenin D, Resnick M. Suppression of allelic recombination and aneuploidy by cohesin is independent of Chk1 in Saccharomyces cerevisiae. PLoS ONE. 2014;9:e113435 pubmed publisher
    ..In yeast, Chk1, which is a kinase that functions in DNA damage signal transduction, is considered an activator of SCC through DIC...
  9. Pijuan J, María C, Herrero E, Bellí G. Impaired mitochondrial Fe-S cluster biogenesis activates the DNA damage response through different signaling mediators. J Cell Sci. 2015;128:4653-65 pubmed publisher
    ..are compromised at the core ISC system, show Mec1- and Rad53-independent Dun1 activation, whereas both Mec1 and Chk1 are required when the non-core ISC member Iba57 is absent...
  10. Torres J, Schnakenberg S, Zakian V. Saccharomyces cerevisiae Rrm3p DNA helicase promotes genome integrity by preventing replication fork stalling: viability of rrm3 cells requires the intra-S-phase checkpoint and fork restart activities. Mol Cell Biol. 2004;24:3198-212 pubmed
    ..The rrm3 system provides a unique opportunity to learn the fate of forks whose progress is impaired by natural impediments rather than by exogenous DNA damage. ..
  11. Fasullo M, Dong Z, Sun M, Zeng L. Saccharomyces cerevisiae RAD53 (CHK2) but not CHK1 is required for double-strand break-initiated SCE and DNA damage-associated SCE after exposure to X rays and chemical agents. DNA Repair (Amst). 2005;4:1240-51 pubmed
    Saccharomyces cerevisiae RAD53 (CHK2) and CHK1 control two parallel branches of the RAD9-mediated pathway for DNA damage-induced G(2) arrest...
  12. Karumbati A, Wilson T. Abrogation of the Chk1-Pds1 checkpoint leads to tolerance of persistent single-strand breaks in Saccharomyces cerevisiae. Genetics. 2005;169:1833-44 pubmed
    ..Mutants affecting the Chk1-Pds1 metaphase-anaphase checkpoint only suppressed tpp1 apn1 rad1 slow growth...
  13. Caldwell J, Chen Y, Schollaert K, Theis J, Babcock G, Newlon C, et al. Orchestration of the S-phase and DNA damage checkpoint pathways by replication forks from early origins. J Cell Biol. 2008;180:1073-86 pubmed publisher
    ..Thus, oncogene-mediated deregulation of cyclins in the early stages of cancer development could contribute to genomic instability through a deficiency in the forks required to establish the S-phase checkpoint. ..
  14. Clerici M, Baldo V, Mantiero D, Lottersberger F, Lucchini G, Longhese M. A Tel1/MRX-dependent checkpoint inhibits the metaphase-to-anaphase transition after UV irradiation in the absence of Mec1. Mol Cell Biol. 2004;24:10126-44 pubmed
    ..Activation of this checkpoint leads to phosphorylation of the downstream checkpoint kinases Rad53 and Chk1, which are required for Tel1-dependent cell cycle arrest, and their adaptor Rad9...
  15. Fasullo M, Sun M. The Saccharomyces cerevisiae checkpoint genes RAD9, CHK1 and PDS1 are required for elevated homologous recombination in a mec1 (ATR) hypomorphic mutant. Cell Cycle. 2008;7:2418-26 pubmed
    ..The mec1-21 hyper-recombination was partially reduced in rad9, pds1 and chk1 mutants, and abolished in rad52 mutants, suggesting the hyper-recombination results from RAD52-dependent ..
  16. Fiorani P, Reid R, Schepis A, Jacquiau H, Guo H, Thimmaiah P, et al. The deubiquitinating enzyme Doa4p protects cells from DNA topoisomerase I poisons. J Biol Chem. 2004;279:21271-81 pubmed
    ..Additional studies suggest a role for Doa4p in the Rad9p checkpoint response to Top1p poisons. These findings indicate a functional link between ubiquitin-mediated proteolysis and cellular resistance to CPT-induced DNA damage. ..
  17. Gobbini E, Villa M, Gnugnoli M, Menin L, Clerici M, Longhese M. Sae2 Function at DNA Double-Strand Breaks Is Bypassed by Dampening Tel1 or Rad53 Activity. PLoS Genet. 2015;11:e1005685 pubmed publisher
    ..We propose that persistent Tel1 and Rad53 checkpoint signaling in cells lacking Sae2 increases the association of Rad9 at DSBs, which in turn inhibits DSB resection by limiting the activity of the Sgs1-Dna2 resection machinery. ..
  18. Pereira E, Chen Y, Sanchez Y. Conserved ATRMec1 phosphorylation-independent activation of Chk1 by single amino acid substitution in the GD domain. Cell Cycle. 2009;8:1788-93 pubmed
    b>Chk1 is a conserved kinase that comprises the first line of defense against DNA damage and replication blocks...
  19. Heidinger Pauli J, Unal E, Koshland D. Distinct targets of the Eco1 acetyltransferase modulate cohesion in S phase and in response to DNA damage. Mol Cell. 2009;34:311-21 pubmed publisher
    ..We show that Mcd1p and Smc3p acetylation antagonize Wpl1p only in their proper context. Thus, Eco1p antagonizes Wpl1p in distinct ways to modulate cohesion generation during the cell cycle and after DNA damage. ..
  20. Liu Y, Vidanes G, Lin Y, Mori S, Siede W. Characterization of a Saccharomyces cerevisiae homologue of Schizosaccharomyces pombe Chk1 involved in DNA-damage-induced M-phase arrest. Mol Gen Genet. 2000;262:1132-46 pubmed
    b>Chk1 is an evolutionarily conserved protein kinase that plays an essential role in mediating G2 arrest in response to DNA damage in Schizosaccharomyces pombe and human cells...
  21. Dotiwala F, Harrison J, Jain S, Sugawara N, Haber J. Mad2 prolongs DNA damage checkpoint arrest caused by a double-strand break via a centromere-dependent mechanism. Curr Biol. 2010;20:328-32 pubmed publisher
    ..Thus, a single DSB triggers a response by both checkpoints to prevent the segregation of a damaged chromosome. ..
  22. Kile A, Koepp D. Activation of the S-phase checkpoint inhibits degradation of the F-box protein Dia2. Mol Cell Biol. 2010;30:160-71 pubmed publisher
    ..Together, our results suggest that Dia2 protein turnover does not involve an autocatalytic mechanism and that Dia2 proteolysis is inhibited by activation of the replication stress response. ..
  23. Grandin N, Charbonneau M. Budding yeast 14-3-3 proteins contribute to the robustness of the DNA damage and spindle checkpoints. Cell Cycle. 2008;7:2749-61 pubmed
    ..the 14-3-3 response was additive with those provided by the Mec1 (ATR-related)-controlled Rad53 (CHK2-related) and Chk1 (CHK1-related) checkpoint pathways and also distinct from the PKA (Protein Kinase A)-controlled response...
  24. Liang F, Wang Y. DNA damage checkpoints inhibit mitotic exit by two different mechanisms. Mol Cell Biol. 2007;27:5067-78 pubmed
    ..In response to DNA damage, two branches of the DNA damage checkpoint, Chk1 and Rad53, are activated in budding yeast to prevent anaphase entry and mitotic exit, allowing cells more time to ..
  25. Gabrielse C, Miller C, McConnell K, DeWard A, Fox C, Weinreich M. A Dbf4p BRCA1 C-terminal-like domain required for the response to replication fork arrest in budding yeast. Genetics. 2006;173:541-55 pubmed
    ..Rad53p likely directly phosphorylated Dbf4p in response to RF arrest and Dbf4p was required for Rad53p abundance. Rad53p and Dbf4p therefore cooperated to coordinate a robust cellular response to RF arrest. ..
  26. Myung K, Pennaneach V, Kats E, Kolodner R. Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability. Proc Natl Acad Sci U S A. 2003;100:6640-5 pubmed
    ..These results indicate that coupling of chromatin assembly to DNA replication and DNA repair is critical to maintaining genome stability. ..
  27. Kim J, Haber J. Chromatin assembly factors Asf1 and CAF-1 have overlapping roles in deactivating the DNA damage checkpoint when DNA repair is complete. Proc Natl Acad Sci U S A. 2009;106:1151-6 pubmed publisher
    ..We suggest that CAF-1 and Asf1 function redundantly to deactivate the checkpoint by restoring chromatin structure on the completion of DSB repair. ..
  28. Abreu C, Kumar R, Hamilton D, Dawdy A, Creavin K, Eivers S, et al. Site-specific phosphorylation of the DNA damage response mediator rad9 by cyclin-dependent kinases regulates activation of checkpoint kinase 1. PLoS Genet. 2013;9:e1003310 pubmed publisher
    ..that the integrity of CDK consensus sites and the activity of Cdc28 are required for both the activation of the Chk1 checkpoint kinase and its interaction with Rad9...
  29. Banerjee S, Myung K. Increased genome instability and telomere length in the elg1-deficient Saccharomyces cerevisiae mutant are regulated by S-phase checkpoints. Eukaryot Cell. 2004;3:1557-66 pubmed
  30. Oh J, Hyun J, Varshavsky A. Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N-end rule pathway. Proc Natl Acad Sci U S A. 2017;114:E4370-E4379 pubmed publisher
    ..b>Chk1, a mitotic checkpoint kinase and a client of Hsp90, was degraded relatively slowly in wild-type cells but was ..