Checking in on Cds1 (Chk2): A checkpoint kinase and tumor suppressor.
Together, DNA repair and checkpoint responses ensure the integrity of the genome. Coordination of cell cycle checkpoints and DNA repair are especially important following genotoxic radiation or chemotherapy, during which unusually high loads of DNA damage are sustained. In mammalian cells, the checkpoint kinase, Cds1 (also known as Chk2) is activated by ATM in response to DNA damage. The role of Cds1 as a checkpoint kinase depends on its ability to phosphorylate cell cycle regulators such p53, Cdc25 and Brca1. A role for Cds1 in repair is suggested by the finding that it interacts with the Holliday junction resolving activity Mus81. This review focuses on the many questions generated by recent progress in understanding the function and regulation of human Cds1.
McGowan
Clare H
CH
Department of Molecular Biology, The Scripps Research Institute, 10550, Torrey Pines Road, La Jolla, California 92037, USA. chmcg@scripps.edu
D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism; D002460:Cell Line; D064447:Checkpoint Kinase 2; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases; D016195:G2 Phase; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D016196:S Phase; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins; D013997:Time Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D020687:cdc25 Phosphatases / Q000378:metabolism
D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; C578636:Cds1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D004720:Endonucleases; C411624:MUS81 protein, S cerevisiae; C498772:MUS81 protein, human; D020687:cdc25 Phosphatases