Checkpoint Kinase 1 (Chk1)

Checkpoint Kinase 1 (Chk1, CHEK1) is a serine/threonine kinase that transduces the ATR-dependent replication stress and DNA damage checkpoint. Activated by ATR-mediated phosphorylation, Chk1 phosphorylates CDC25A, CDC25C, WEE1 and other substrates, enforcing S phase and G2/M arrest while homologous recombination repairs damaged DNA. Mouse embryos lacking Chk1 die early, underlining its essential role in genome maintenance. Because tumors with high replication stress are selectively vulnerable to checkpoint abrogation, Chk1 inhibitors have been combined with genotoxic chemotherapy and ATR inhibitors in oncology trials.