Dept of Molecular Biology University of Wyoming, Laramie, WY 82071, USA.
J Biomol Struct Dyn. 2010 Feb;27(4):399-406. doi: 10.1080/07391102.2010.10507326.
BRCA1, the protein product of the Breast Cancer Susceptibility Gene (BRCA1) has been implicated in multiple pathways that preserve genome stability, including cell cycle control, DNA repair, transcription, and chromatin remodeling. BRCA1, in complex with another RING-domain protein BARD1, possesses ubiquitin-ligase activity. Only a few targets for this activity have been identified in vivo. Nucleosomal histones may also be targets in vivo since they can be modified by the BRCA1/BARD1 complex in vitro. Here we demonstrate that the BRCA1/BARD1 complex can ubiquitylate both free H2A and H2B histones and histones in the context of nucleosomal particles. These results raise the possibility that BRCA1/BARD1 can directly affect nucleosomal structure, dynamics, and function through its ability to modify nucleosomal histones.
BRCA1 蛋白是乳腺癌易感基因（BRCA1）的产物，它参与了多种维持基因组稳定性的途径，包括细胞周期控制、DNA 修复、转录和染色质重塑。BRCA1 与另一个 RING 结构域蛋白 BARD1 形成复合物，具有泛素连接酶活性。在体内仅鉴定出这种活性的少数几个靶标。核小体组蛋白也可能是体内的靶标，因为它们可以在体外被 BRCA1/BARD1 复合物修饰。在这里，我们证明 BRCA1/BARD1 复合物可以泛素化游离的 H2A 和 H2B 组蛋白以及核小体颗粒中的组蛋白。这些结果表明，BRCA1/BARD1 可以通过修饰核小体组蛋白直接影响核小体结构、动力学和功能。
