Role of BRCT motif containing proteins in Chk1 activation

Excerpt

Chk1, along with Chk2, regulates processes such as DNA replication, cell cycle control, chromatin restructuring and apoptosis. DNA damage/replication stress activates Chk1 by phosphorylation from the PI3/PI4 family of kinases. Activation of Chk1 is thought to be mediated by proteins containing the BRCA1 C-terminal domain (BRCT). We previously identified a potential complex of four Chk1-associated proteins by immunoprecipitation, western blotting and mass spectrometry, one of which is BRCA1. Germline mutations in BRCA1 are responsible for many cases of hereditary breast cancer, and cells deficient in BRCA1 sustain spontaneous aberrations in chromosome structure. Such findings indicate that BRCA1 is essential for suppressing genome instability. …