BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.
BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.
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DOI：
10.1101/gad.14.8.927
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发表时间：
2000-04
影响因子：
10.5
通讯作者：
Yi Wang;D. Cortez;P. Yazdi;N. Neff;S. Elledge;J. Qin
中科院分区：
文献类型：
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作者：
Yi Wang;D. Cortez;P. Yazdi;N. Neff;S. Elledge;J. Qin
我们报告了与BRCA1相关的一组蛋白质成员的身份，这些蛋白质形成了一个大的复合体，我们将其命名为BASC （BRCA1相关基因组监视复合体）。该复合体包括肿瘤抑制因子和DNA损伤修复蛋白MSH2、MSH6、MLH1、ATM、BLM和RAD50-MRE11-NBS1蛋白复合体。此外，DNA复制因子C (RFC)，一种促进PCNA装载到DNA上的蛋白质复合体，也是BASC的一部分。我们发现当细胞被干扰DNA合成的药物处理时，BRCA1、BLM解旋酶和RAD50-MRE11-NBS1复合体共定位到含有PCNA的大核病灶。BRCA1与转录偶联修复所需的MSH2和MSH6的关联为BRCA1在这一途径中的作用提供了可能的解释。引人注目的是，该复合体的所有成员都在识别异常DNA结构或受损DNA中发挥作用，这表明BASC可能作为DNA损伤的传感器。其中一些蛋白质也在DNA复制相关修复中发挥作用。总之，这些结果表明，BRCA1可能在DNA复制过程中作为维持基因组完整性所需的多种活动的协调者，并指出BRCA1在DNA修复中起核心作用。
We report the identities of the members of a group of proteins that associate with BRCA1 to form a large complex that we have named BASC (BRCA1-associated genome surveillance complex). This complex includes tumor suppressors and DNA damage repair proteins MSH2, MSH6, MLH1, ATM, BLM, and the RAD50-MRE11-NBS1 protein complex. In addition, DNA replication factor C (RFC), a protein complex that facilitates the loading of PCNA onto DNA, is also part of BASC. We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. The association of BRCA1 with MSH2 and MSH6, which are required for transcription-coupled repair, provides a possible explanation for the role of BRCA1 in this pathway. Strikingly, all members of this complex have roles in recognition of abnormal DNA structures or damaged DNA, suggesting that BASC may serve as a sensor for DNA damage. Several of these proteins also have roles in DNA replication-associated repair. Collectively, these results suggest that BRCA1 may function as a coordinator of multiple activities required for maintenance of genomic integrity during the process of DNA replication and point to a central role for BRCA1 in DNA repair.