Chk2 Phosphorylation of BRCA1 Regulates DNA Double-Strand Break Repair

• DOI: 10.1128/mcb.24.2.708-718.2004
• Publication Date: 2003-12-31T01:03:50Z
• Authors: Junran Zhang; Henning Willers; Zhihui Feng; Jagadish C. Ghosh; Sang Kim; David T. Weaver; Jay H. Chung; Simon N. Powell; Fen Xia
• Keywords: Non-homologous end joining; Homology directed repair

The pathway determining malignant cellular transformation, which depends upon mutation of the BRCA1 tumor suppressor gene, is poorly defined. A growing body evidence suggests that promotion DNA double-strand break repair by homologous recombination (HR) may be means maintains genomic stability, while a role in error-prone nonhomologous (NHR) processes has just begun to elucidated. protein becomes phosphorylated response damage, but effects phosphorylation on recombinational are unknown. In this study, we tested hypothesis BRCA1-mediated regulation requires Chk2- and ATM-dependent sites. We studied Rad51-dependent HR random chromosomal integration linearized plasmid DNA, subtype NHR, demonstrate dependent Mre11-Rad50-Nbs1 complex. Prevention Chk2-mediated via serine 988 residue disrupted both BRCA1-dependent suppression NHR. Similar results were obtained when endogenous Chk2 kinase activity was inhibited expression dominant-negative mutant. Surprisingly, opposing NHR did not require ATM sites serines 1423 1524. Together, these data suggest functional link between control breast cancer predisposition carriers germ line mutations. propose dual regulatory for maintaining genome integrity, whereby status controls selectivity events dictated