Progress in role of breast cancer susceptibility gene 1 in DNA damage repair / 中国药理学与毒理学杂志

ABSTRACT

Breast cancer susceptibiIity gene 1( BRCA1)is a tumor suppressor,but mutated get BRCA1 is cIoseIy reIated to the deveIopment of breast cancer. Current study has reveaIed that BRCA1 can get invoIved in the DNA damage repair process as a key mediator. DNA doubIe-stranded break (DSB)is the most serious form in DNA Iesions,and BRCA1 pIays an important roIe in repairing DSB through reguIation of homoIogous recombination( HR). In this articIe,the moIecuIar mechanism of BRCA1 in reguIating HR is reviewed with reference to the activity of functionaI domains in BRCA1 struc-ture,the mutations occurring in main domains of BRCA1,the reIationship of BRCA1 with BRCA2, Rad51 or CtIP,and phosphoryIation of BRCA1. In addition,the association of the defective BRCA1-mediated HR repair mechanism with the sensitivity to different DNA damaging agents and synthetic IethaIity in tumor ceIIs is aIso addressed.