title: Cdk phosphorylation of Chk1 regulates efficient Chk1 activation and multiple checkpoint proficiency.
abstract: It has been reported previously that both Cdk1 and Cdk2 phosphorylate Chk1 in a cell-cycle dependent manner. Cdk-mediated phosphorylation is required for efficient activation of Chk1 and checkpoint proficiency in response to DNA damage. Here, we demonstrate that Cdk-mediated phosphorylation is also required for replication stress induced Chk1 activation and S/M checkpoint proficiency. Re-introduction of Chk1 mutant (S286A/S301A) into Chk1 deficient cells is capable of restraining mitosis in cells with completely unreplicated DNA, but the mitotic delay at later stage of the cell cycle is largely impaired. The mutation strongly attenuates aphidicolin induced Chk1 activation without altering the S-phase dependent Chk1 activation. These data indicate that Cdk-mediated phosphorytion is required for efficient Chk1 activation and multiple checkpoint proficiency.
authors: Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China. xu.naihan@sz.tsinghua.edu.cn
authors: Naihan
authors: N
authors: Xu
authors: Silvana
authors: S
authors: Libertini
authors: Yaou
authors: Y
authors: Zhang
authors: David A
authors: DA
authors: Gillespie
mesh_terms: D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004261:DNA Replication; D004789:Enzyme Activation; D016195:G2 Phase; D006801:Humans; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016196:S Phase
chemical_list: D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D018844:Cyclin-Dependent Kinases