BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair.
BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair.
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DOI：
10.1016/j.molcel.2012.02.015
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发表时间：
2012-04-27
期刊：
影响因子：
16
通讯作者：
Nussenzweig, Andre
中科院分区：
文献类型：
--
作者：
Bunting, Samuel F.;Callen, Elsa;Kozak, Marina L.;Kim, Jung Min;Wong, Nancy;Lopez-Contreras, Andres J.;Ludwig, Thomas;Baer, Richard;Faryabi, Robert B.;Malhowski, Amy;Chen, Hua-Tang;Fernandez-Capetillo, Oscar;D'Andrea, Alan;Nussenzweig, Andre
Brca1是通过同源重组修复DNA和正常胚胎发育所必需的。在这里，我们报告了DNA损伤反应因子53BP1的缺失克服了brca1无合子小鼠的胚胎致死性，并通过对PARP（聚adp核糖聚合酶）抑制的超敏性来挽救HR缺陷。然而，Brca1,53BP1双缺陷细胞对DNA链间交联（ICLs）敏感，这表明Brca1在DNA交联修复中具有不同于HR的额外作用。非同源末端连接（NHEJ）因子Ku的破坏促进brca1缺陷细胞的DNA修复；然而，Ku或53BP1的缺失加剧了缺乏FANCD2的细胞的基因组不稳定性，FANCD2是ICL修复的范可尼贫血途径的中介。因此，BRCA1在ICL修复中有两个独立的作用，而FANCD2提供了一个不能被53BP1或Ku消融绕过的关键活性。
Brca1 is required for DNA repair by homologous recombination (HR) and normal embryonic development. Here we report that deletion of the DNA damage response factor 53BP1 overcomes embryonic lethality in Brca1-nullizygous mice, and rescues HR deficiency, as measured by hypersensitivity to PARP (polyADP-ribose polymerase) inhibition. However, Brca1,53BP1 double-deficient cells are hypersensitive to DNA interstrand cross-links (ICLs), indicating that BRCA1 has an additional role in DNA cross-link repair that is distinct from HR. Disruption of the non-homologous end-joining (NHEJ) factor, Ku, promotes DNA repair in Brca1-deficient cells; however deletion of either Ku or 53BP1 exacerbates genomic instability in cells lacking FANCD2, a mediator of the Fanconi Anemia pathway for ICL repair. BRCA1 therefore has two separate roles in ICL repair, whereas FANCD2 provides a key activity that can not be bypassed by ablation of 53BP1 or Ku.
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影响因子：
3.5
作者：
Houghtaling, S;Newell, A;Grompe, M
通讯作者：
Grompe, M
影响因子：
16
作者：
Bothmer A;Robbiani DF;Di Virgilio M;Bunting SF;Klein IA;Feldhahn N;Barlow J;Chen HT;Bosque D;Callen E;Nussenzweig A;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
4.8
作者：
Bhattacharyya, A;Ear, US;Bishop, DK
通讯作者：
Bishop, DK
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
16
作者：
Garcia-Higuera, I;Taniguchi, T;D'Andrea, AD
通讯作者：
D'Andrea, AD