Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, USA.
Mol Cell Biol. 2011 Oct;31(19):3924-37. doi: 10.1128/MCB.01269-10. Epub 2011 Aug 1.
Homologous recombination repairs DNA double-strand breaks by searching for, invading, and copying information from a homologous template, typically the homologous chromosome or sister chromatid. Tight wrapping of DNA around histone octamers, however, impedes access of repair proteins to DNA damage. To facilitate DNA repair, modifications of histones and energy-dependent remodeling of chromatin are required, but the precise mechanisms by which chromatin modification and remodeling enzymes contribute to homologous DNA repair are unknown. Here we have systematically assessed the role of budding yeast RSC (remodel structure of chromatin), an abundant, ATP-dependent chromatin-remodeling complex, in the cellular response to spontaneous and induced DNA damage. RSC physically interacts with the recombination protein Rad59 and functions in homologous recombination. Multiple recombination assays revealed that RSC is uniquely required for recombination between sister chromatids by virtue of its ability to recruit cohesin at DNA breaks and thereby promoting sister chromatid cohesion. This study provides molecular insights into how chromatin remodeling contributes to DNA repair and maintenance of chromatin fidelity in the face of DNA damage.
同源重组通过搜索、入侵和从同源模板（通常是同源染色体或姐妹染色单体）复制信息来修复 DNA 双链断裂。然而，DNA 紧紧缠绕在组蛋白八聚体周围，阻碍了修复蛋白与 DNA 损伤的接触。为了促进 DNA 修复，需要对组蛋白进行修饰和能量依赖性的染色质重塑，但染色质修饰和重塑酶如何有助于同源 DNA 修复的精确机制尚不清楚。在这里，我们系统地评估了芽殖酵母 RSC（重塑染色质结构）在细胞对自发和诱导的 DNA 损伤的反应中的作用，RSC 是一种丰富的、依赖 ATP 的染色质重塑复合物。RSC 与重组蛋白 Rad59 相互作用，并在同源重组中发挥作用。多项重组实验表明，RSC 通过其在 DNA 断裂处募集黏合蛋白的能力，从而促进姐妹染色单体的黏合，从而独特地需要用于姐妹染色单体之间的重组。这项研究为染色质重塑如何有助于 DNA 修复以及在面对 DNA 损伤时维持染色质保真度提供了分子见解。
