Homology-Directed Repair and the Role of BRCA1, BRCA2, and Related Proteins in Genome Integrity and Cancer.
Homology-Directed Repair and the Role of BRCA1, BRCA2, and Related Proteins in Genome Integrity and Cancer.
复制标题
同源性修复以及BRCA1，BRCA2及其相关蛋白在基因组完整性和癌症中的作用。
DOI：
10.1146/annurev-cancerbio-030617-050502
复制
发表时间：
2018-03
影响因子：
7.7
通讯作者：
Jasin M
中科院分区：
文献类型：
--
作者：
Chen CC;Feng W;Lim PX;Kass EM;Jasin M
促进同源定向修复（HDR）的基因（尤其是BRCA 1和BRCA 2）中的生殖系和体细胞突变经常在几种癌症中观察到，特别是乳腺癌和卵巢癌，还有前列腺癌和其他癌症。HDR对于DNA双链断裂和其他病变的无错误修复至关重要，HDR因子还保护停滞的复制叉。因此，BRCA 1或BRCA 2的缺失对基因组完整性构成重大风险，不仅导致癌症易感性，而且导致对DNA损伤剂的敏感性，影响治疗方法。在这里，我们回顾了我们对BRCA 1和BRCA 2的理解的最新进展，包括它们如何与其他修复因子发生遗传相互作用，它们如何保护停滞的复制叉，它们如何影响对醛的反应，以及它们的功能丧失如何与突变特征联系起来。重要的是，鉴于聚（ADP-核糖）聚合酶抑制剂（PARPi）治疗HDR缺陷型肿瘤的最新进展，我们讨论了BRCA缺陷型肿瘤对PARPi和其他药物产生耐药性的机制。
Germ-line and somatic mutations in genes that promote homology-directed repair (HDR), especially BRCA1 and BRCA2, are frequently observed in several cancers, in particular, breast and ovary but also prostate and other cancers. HDR is critical for the error-free repair of DNA double-strand breaks and other lesions, and HDR factors also protect stalled replication forks. As a result, loss of BRCA1 or BRCA2 poses significant risks to genome integrity, leading not only to cancer predisposition but also to sensitivity to DNA-damaging agents, affecting therapeutic approaches. Here we review recent advances in our understanding of BRCA1 and BRCA2, including how they genetically interact with other repair factors, how they protect stalled replication forks, how they affect the response to aldehydes, and how loss of their functions links to mutation signatures. Importantly, given the recent advances with poly(ADP-ribose) polymerase inhibitors (PARPi) for the treatment of HDR-deficient tumors, we discuss mechanisms by which BRCA-deficient tumors acquire resistance to PARPi and other agents.
登录
查看更多内容
DOI：
10.1158/1078-0432.ccr-16-2174
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Afghahi A;Timms KM;Vinayak S;Jensen KC;Kurian AW;Carlson RW;Chang PJ;Schackmann E;Hartman AR;Ford JM;Telli ML
通讯作者：
Telli ML
影响因子：
4.7
作者：
Caldon CE
通讯作者：
Caldon CE
影响因子：
14.9
作者：
Bakr A;Oing C;Köcher S;Borgmann K;Dornreiter I;Petersen C;Dikomey E;Mansour WY
通讯作者：
Mansour WY
影响因子：
4
作者：
Chapman, J. Ross;Sossick, Alex J.;Jackson, Stephen P.
通讯作者：
Jackson, Stephen P.
影响因子：
7.7
作者：
Anantha, Rachel W.;Simhadri, Srilatha;Xia, Bing
通讯作者：
Xia, Bing