Checkpoint kinase 1 (CHK1)

CHK1 is a master regulator of the DNA damage response (DDR) and cell cycle checkpoints in eukaryotic cells. It plays essential roles in initiating and maintaining cell cycle arrest, stabilizing stalled replication forks, and phosphorylating key regulators like CDK1. CHK1 is a validated clinical trial target with particular relevance in oncology, as its inhibition can sensitize p53-deficient cancer cells to genotoxic therapies.

Other names

Cell cycle checkpoint kinaseCHK1 checkpoint homologSerine/threonine-protein kinase Chk1CHEK1

CHK1 activation primarily occurs via phosphorylation by the upstream regulatory kinase ATR. Upon activation, CHK1 phosphorylates downstream substrates involved in cell cycle control. In unperturbed cycles, it regulates normal progression through S phase, G2/M transition, and M phase. In response to genotoxic stress or DNA damage, it triggers checkpoints that halt the cell cycle for repair processes. If repair fails or damage is excessive, it can lead to programmed cell death (apoptosis).