... that a previously unrecognised balance between the cyclin-dependent kinase (CDK) inhibitor p21 and the checkpoint kinase Chk1 controls cyclin D–CDK activity during G2 arrest. In non-transformed cells, p21 activates RB in G2 by inhibiting cyclin D1 complexed with CDK2 or CDK4. The resulting G2 exit, which precedes...

... downregulated multiple key targets in the DNA damage response (DDR) pathway, namely BRCA1, ATM, Chk1 (also known as CHEK1) and RNF8. CDX2 directly regulated the DDSMs, which led to increased tumor volume and metastasis in multiple preclinical models. In colon cancer patient tissues, the DDSMs negatively...

...Hidemasa Goto; Toyoaki Natsume; Masato T. Kanemaki; Aika Kaito; Shujie Wang; Esteban C. Gabazza; Masaki Inagaki; Akira Mizoguchi ABSTRACT Chk1 (encoded by CHEK1 in mammals) is an evolutionarily conserved protein kinase that transduces checkpoint signals from ATR to Cdc25A during the DNA damage...

...Kévin Adam; Maëlle Cartel; Mireille Lambert; Laure David; Lingli Yuan; Arnaud Besson; Patrick Mayeux; Stéphane Manenti; Christine Didier ABSTRACT Although the kinase CHK1 is a key player in the DNA damage response (DDR), several studies have recently provided evidence of DDR-independent roles...

... in PARP-1 activity in CDA-deficient cells impairs DNA-damage-induced Chk1 activation, and, thus, the downstream checkpoints. Chemical inhibition of the ATR–Chk1 pathway leads to UFB accumulation, and we found that this pathway was compromised in CDA-deficient cells. Our data demonstrate that ATR–Chk1 acts...

... of chromatin bridges. Here, we show that cells deficient in checkpoint kinase 1 (Chk1, also known as CHEK1) exhibit higher frequency of chromatin bridges and reduced BLM protein levels compared to controls. Chk1 inhibition leads to BLM ubiquitylation and proteasomal degradation during interphase. Furthermore...

...Daniël O. Warmerdam; Eva K. Brinkman; Jurgen A. Marteijn; René H. Medema; Roland Kanaar; Veronique A. J. Smits Summary In response to UV light, single-stranded DNA intermediates coated with replication protein A (RPA) are generated, which trigger the ATR-Chk1 checkpoint pathway. Recruitment...

...Eleni Petsalaki; George Zachos Summary If uncorrected, merotelic kinetochore attachments can induce mis-segregated chromosomes in anaphase. We show that checkpoint kinase 1 (Chk1) protects vertebrate cells against merotelic attachments and lagging chromosomes and is required for correction...

...Makoto Matsuyama; Hidemasa Goto; Kousuke Kasahara; Yoshitaka Kawakami; Makoto Nakanishi; Tohru Kiyono; Naoki Goshima; Masaki Inagaki 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...

... predominantly by Chk1 and weakly by Chk2 at S408 in vivo, and that this process occurs at all stages of the cell cycle and leads to phosphorylation of 14-3-3γ on S59 by Lats2. Interaction of Lats2 and 14-3-3γ in vivo was confirmed by immunoprecipitation and western blot analysis. Phosphorylated 14-3-3γ...

...-expressing the eIF2α phosphatase GADD34. A genetic screen of 3000 transposon insertions identified grapes , the gene that encodes the Drosophila orthologue of checkpoint kinase 1 (CHK1). Knockdown of grapes by RNAi rescued eye development despite ongoing PERK activation. In mammalian cells, CHK1...

.... Sequestration in the cytoplasm of the Cdc25 phosphatase seems to be one of the reasons for the increase in inhibitory phosphorylation. Strikingly, we also report the DNA-damage checkpoint kinase Chk1 appears to be involved in this process. Our results support the emerging idea that checkpoint kinases have roles...

... and persistent activation of Rad53. Moreover, because ccr4 Δ and chk1 Δ exhibited epistasis in several genetic contexts, we infer that Ccr4 and Chk1 act in the same pathway to overcome replication stress. A counterscreen for suppressors of ccr4 Δ HU sensitivity uncovered mutations in CRT1 , which encodes...

... on the activation of a centrosomal pool of CDK1–cyclin-B1, and CDC25B is thought to be involved in initiating this centrosomal CDK1–cyclin-B1 activity. 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...

... in the cell cycle at which radiation is applied, which may explain the apparent differences among experimental systems and offer an explanation as to why this regulation has not been seen in mammalian cells. We further document that mutants in Drosophila Chk1 (Grapes) that are capable of delaying the progress...

... for checkpoint signalling, Chk1 and Chk2 are structurally conserved. In contrast to yeast, Xenopus and mammals, the Chk1- and Chk2-dependent pathways in Drosophila are not understood in detail. Here, we report the function of these checkpoint kinases, referred to as Grp/DChk1 and Dmnk/DChk2 in Drosophila...

..., the latter being predominant in G2 phase of the cell cycle. The p53-independent pathway involves a phosphorylation cascade that activates the Chk1 effector kinase and induces G2 arrest through inhibitory tyrosine phosphorylation of Cdc2. At the top of this cascade are the ATR and ATM kinases. How ATM and ATR...

...Stephen Dunaway; Hsing-Yin Liu; Nancy C. Walworth The protein kinase Chk1 is required for proper arrest of the cell cycle in response to DNA damage. We have previously shown in Schizosaccharomyces pombe , that upon DNA damage, phosphorylation of Chk1 correlates with checkpoint activation...

... yeast Schizosaccharomyces pombe . Rad3 activates the effector protein kinase Chk1 by phosphorylation. However, in fission yeast, inactivation of Rad3 following checkpoint activation has no impact on checkpoint duration. This demonstrates that Rad3 is not required for checkpoint maintenance...

...Richard T. Blankley; David Lydall The Rad9 protein is a key adaptor protein in Saccharomyces cerevisiae DNA damage checkpoint pathways. Its adaptor function is to link the activity of the Mec1 kinase to the activation of two parallel signalling pathways dependent on the Rad53 and Chk1 kinases...