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解析 BRCA2 在同源重组中的作用机制。

Unraveling the mechanism of BRCA2 in homologous recombination.

机构信息

Department of Microbiology and Immunology, Weill Cornell Cancer Center, Weill Cornell Medical College, New York, New York, USA.

出版信息

Nat Struct Mol Biol. 2011 Jul 6;18(7):748-54. doi: 10.1038/nsmb.2096.

DOI:10.1038/nsmb.2096
PMID:21731065
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3647347/
Abstract

BRCA2 is the product of a breast cancer susceptibility gene in humans and the founding member of an emerging family of proteins present throughout the eukaryotic domain that serve in homologous recombination. The function of BRCA2 in recombination is to control RAD51, a protein that catalyzes homologous pairing and DNA strand exchange. By physically interacting with both RAD51 and single-stranded DNA, BRCA2 mediates delivery of RAD51 preferentially to sites of single-stranded DNA (ssDNA) exposed as a result of DNA damage or replication problems. Through its action, BRCA2 helps restore and maintain integrity of the genome. This review highlights recent studies on BRCA2 and its orthologs that have begun to illuminate the molecular mechanisms by which these proteins control homologous recombination.

摘要

BRCA2 是人类乳腺癌易感基因的产物,也是一个新兴蛋白家族的创始成员,该家族蛋白存在于真核生物域中,在同源重组中发挥作用。BRCA2 在重组中的功能是控制 RAD51,RAD51 是一种催化同源配对和 DNA 链交换的蛋白质。通过与 RAD51 和单链 DNA 的物理相互作用,BRCA2 介导 RAD51 优先递送到由于 DNA 损伤或复制问题而暴露的单链 DNA(ssDNA)部位。通过其作用,BRCA2 有助于恢复和维持基因组的完整性。本综述重点介绍了最近关于 BRCA2 及其同源物的研究,这些研究开始阐明这些蛋白质控制同源重组的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94de/3647347/a7a3faec8255/nihms-464643-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94de/3647347/17ec96690e4c/nihms-464643-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94de/3647347/a7a3faec8255/nihms-464643-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94de/3647347/17ec96690e4c/nihms-464643-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94de/3647347/a7a3faec8255/nihms-464643-f0002.jpg

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本文引用的文献

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Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11.BRCA2 在阻止 MRE11 降解停滞复制叉中的双链断裂修复非依赖性作用。
Cell. 2011 May 13;145(4):529-42. doi: 10.1016/j.cell.2011.03.041.
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Who's who in human recombination: BRCA2 and RAD52.人类重组中的关键角色:BRCA2和RAD52
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):441-2. doi: 10.1073/pnas.1016614108. Epub 2010 Dec 28.
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Mutational analysis of Brh2 reveals requirements for compensating mediator functions.Brh2 突变分析揭示了补偿中介体功能的要求。
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Predictive modeling of gene mutations for the survival outcomes of epithelial ovarian cancer patients.预测上皮性卵巢癌患者基因突变与生存结局的关系。
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10
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Nat Struct Mol Biol. 2010 Oct;17(10):1263-5. doi: 10.1038/nsmb.1905. Epub 2010 Aug 22.