复制蛋白 A 在 BLM-Topo IIIα-RMI1-RMI2 蛋白复合物介导的双链 Holliday 连接点溶解中的作用。
Role of replication protein A in double holliday junction dissolution mediated by the BLM-Topo IIIα-RMI1-RMI2 protein complex.
机构信息
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520.
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520.
出版信息
J Biol Chem. 2013 May 17;288(20):14221-14227. doi: 10.1074/jbc.M113.465609. Epub 2013 Mar 30.
Abstract
The conserved BTR complex, composed of the Bloom's syndrome helicase (BLM), topoisomerase IIIα, RMI1, and RMI2, regulates homologous recombination in favor of non-crossover formation via the dissolution of the double Holliday Junction (dHJ). Here we show enhancement of the BTR-mediated dHJ dissolution reaction by the heterotrimeric single-stranded DNA binding protein replication protein A (RPA). Our results suggest that RPA acts by sequestering a single-stranded DNA intermediate during dHJ dissolution. We provide evidence that RPA physically interacts with RMI1. The RPA interaction domain in RMI1 has been mapped, and RMI1 mutants impaired for RPA interaction have been generated. Examination of these mutants ascertains the significance of the RMI1-RPA interaction in dHJ dissolution. Our results thus implicate RPA as a cofactor of the BTR complex in dHJ dissolution.
摘要
BTR 复合体由布卢姆综合征解旋酶 (BLM)、拓扑异构酶 IIIα、RMI1 和 RMI2 组成，通过溶解双链 Holliday 结 (dHJ)，促进有利于非交叉形成的同源重组。在这里，我们显示异源三聚体单链 DNA 结合蛋白复制蛋白 A (RPA)增强了 BTR 介导的 dHJ 溶解反应。我们的结果表明，RPA 通过在 dHJ 溶解过程中隔离单链 DNA 中间体来发挥作用。我们提供了证据表明 RPA 与 RMI1 发生物理相互作用。已经确定了 RMI1 中的 RPA 相互作用结构域，并生成了 RPA 相互作用缺陷的 RMI1 突变体。对这些突变体的检查确定了 RMI1-RPA 相互作用在 dHJ 溶解中的重要性。因此，我们的结果表明 RPA 是 BTR 复合体在 dHJ 溶解中的辅助因子。
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