Department of Microbiology and Molecular Genetics, University of California, Davis, CA 95616, USA.
Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
Genes (Basel). 2021 Aug 10;12(8):1229. doi: 10.3390/genes12081229.
The tumor suppressor BRCA2 functions as a central caretaker of genome stability, and individuals who carry BRCA2 mutations are predisposed to breast, ovarian, and other cancers. Recent research advanced our mechanistic understanding of BRCA2 and its various interaction partners in DNA repair, DNA replication support, and DNA double-strand break repair pathway choice. In this review, we discuss the biochemical and structural properties of BRCA2 and examine how these fundamental properties contribute to DNA repair and replication fork stabilization in living cells. We highlight selected BRCA2 binding partners and discuss their role in BRCA2-mediated homologous recombination and fork protection. Improved mechanistic understanding of how BRCA2 functions in genome stability maintenance can enable experimental evidence-based evaluation of pathogenic BRCA2 mutations and BRCA2 pseudo-revertants to support targeted therapy.
抑癌基因 BRCA2 作为基因组稳定性的中央守护者发挥作用，携带 BRCA2 突变的个体易患乳腺癌、卵巢癌和其他癌症。最近的研究增进了我们对 BRCA2 及其在 DNA 修复、DNA 复制支持和 DNA 双链断裂修复途径选择中各种相互作用伙伴的机制理解。在这篇综述中，我们讨论了 BRCA2 的生化和结构特性，并探讨了这些基本特性如何有助于活细胞中的 DNA 修复和复制叉稳定。我们强调了选定的 BRCA2 结合伙伴，并讨论了它们在 BRCA2 介导的同源重组和叉保护中的作用。对 BRCA2 如何在维持基因组稳定性方面发挥作用的机制理解的提高，可以为基于实验证据的致病性 BRCA2 突变和 BRCA2 伪回复变体的评估提供支持，从而支持靶向治疗。
