Chk1 promotes non-homologous end joining in G1 through direct phosphorylation of ASF1A.

ABSTRACT: The cell-cycle phase is a major determinant of repair pathway choice at DNA double strand breaks, non-homologous end joining (NHEJ), or homologous recombination (HR). Chk1 responds to genotoxic stress in S/G2 phase, but here, we report a role of Chk1 in directly promoting NHEJ repair in G1 phase. ASF1A is a histone chaperone, but it promotes NHEJ through a pathway independent of its histone-chaperone activity. Chk1 activated by ataxia telangiectasia mutated (ATM) kinase on DNA breaks in G1 promotes NHEJ through direct phosphorylation of ASF1A at Ser-166. ASF1A phosphorylated at Ser-166 interacts with the repair protein MDC1 and thus enhances MDC1's interaction with ATM and the stable localization of ATM at DNA breaks. Chk1 deficiency suppresses all steps downstream of MDC1 following a DNA

SUBMITTER: Lee KY 

PROVIDER: S-EPMC7941734 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature