BRCA1介导的DNA重组修复与肿瘤抑制的新进展。
New twist on BRCA1-mediated DNA recombination repair and tumor suppression.
作者信息
Zong Dali, Pavani Raphael, Nussenzweig André
机构信息
Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
出版信息
Trends Cell Biol. 2025 Jun 5. doi: 10.1016/j.tcb.2025.05.002.
Ever since BRCA1 germline mutations were found to confer a strong predisposition to the development of breast and ovarian cancers, there has been great interest in determining how this protein suppresses tumor formation. Through more than two decades of research, it has become clear that BRCA1 safeguards our genome mainly by promoting DNA repair through homologous recombination (HR). This opinion article outlines our evolving view of BRCA1's role in end resection, an upstream commitment step for HR, and highlights recent discoveries suggesting that the context in which DNA breaks are generated dictates whether BRCA1 is required for end resection. In addition, strong emerging evidence for the tumor-suppressive function of BRCA1 being mediated predominantly by its indispensable role in supporting RAD51-dependent recombination downstream of end resection is discussed.
自从发现BRCA1种系突变会大大增加患乳腺癌和卵巢癌的易感性以来，人们对确定这种蛋白质如何抑制肿瘤形成产生了浓厚兴趣。经过二十多年的研究，已经明确BRCA1主要通过促进同源重组（HR）进行DNA修复来保护我们的基因组。这篇观点文章概述了我们对BRCA1在末端切除（HR的上游关键步骤）中作用的不断演变的看法，并强调了最近的发现，即DNA断裂产生的背景决定了末端切除是否需要BRCA1。此外，还讨论了强有力的新证据，表明BRCA1的肿瘤抑制功能主要是由其在支持末端切除下游的RAD51依赖性重组中不可或缺的作用介导的。
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