BRCA1与DNA损伤修复调控网络

BRCA1 and DNA damage response

DNA损伤应答机制的存在有助于机体基因组稳定性的维持.BRCA1是一种重要的肿瘤抑制基因,它在DNA损伤应答中发挥了重要的作用.BRCA1可以与BARD1结合形成稳定的异源二聚体,作为BRCA1复合体蛋白组分的核心参与了DNA损伤信号传递、同源重组修复、DNA复制、细胞周期等多途径的调控.本文主要对BRCA1功能及其参与DNA损伤应答网络调控展开阐述,并总结了利用PARP抑制剂针对BRCA1突变肿瘤进行治疗产生耐药性的多种机制.

DNA damage response contributes to the maintenance of genomic stability in individuals.As an important tumor suppressor gene,BRCA1 plays a crucial role in DNA damage response.BRCA1 upon binding to BARD1 forms a stable heterodimer which is the core component of BRCA1 functional complex.BRCA1 takes part in the regulation of DNA damage signaling transduction,homologous recombination,DNA replication,and cell cycle.In this review,we have described BRCA1’s function and its involvement in the regulation of DNA damage response network.Furthermore,we have summarized the various mechanisms of PARP inhibitors’resistance in tumors with BRCA1 mutated.