Expanded roles for Chk1 in genome maintenance.
Chk1 is a conserved kinase that imposes cell cycle delays in response to impediments to DNA replication. Recent experiments have further defined effects of Chk1 on the activity of mammalian origins of DNA replication and progression of replication forks. Moreover, Chk1 now appears to help defend genomic integrity through effects on several other pathways, including Fanconi anemia proteins, the mitotic spindle, and transcription of cell cycle-related genes. These findings can account for the requirement for Chk1 in normal proliferating cells of the early embryo and suggest the potential for diverse effects of Chk1 inhibition in cancer therapy.
Enders
Greg H
GH
Department of Medicine, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Greg.Enders@fccc.edu
D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D002645:Chickens; D004247:DNA / Q000378:metabolism; D004261:DNA Replication; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D008941:Spindle Apparatus
D004247:DNA; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1