Overlapping Roles for Yen1 and Mus81 in Cellular Holliday Junction Processing
Overlapping Roles for Yen1 and Mus81 in Cellular Holliday Junction Processing
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DOI：
10.1074/jbc.m110.108399
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发表时间：
2010-04-09
影响因子：
4.8
通讯作者：
Wu, Leonard
中科院分区：
文献类型：
--
作者：
Tay, Ye Dee;Wu, Leonard
真核霍利迪连接体 (HJ) 解离酶最近引起了广泛关注，因为鉴定出至少三种可以在体外裂解模型 HJ 的不同蛋白质。然而，这些蛋白质在细胞中作用的具体 DNA 结构尚不清楚。在这里，我们描述了一个在芽殖酵母中直接定量监测体内 HJ 分辨率的系统。我们发现 Yen1 与 Mus81 一起发挥冗余作用，但与 Slx1 无关，以解决体内模型 HJ 的问题。这种功能重叠特别延伸到修复/旁路阻碍复制叉进展的病变，但不延伸到修复电离辐射引起的双链断裂。总之，这些结果表明 Yen1 在 DNA 损伤反应中发挥直接作用，并暗示在复制叉修复过程中 Yen1 与 Mus81 的 HJ 解析功能重叠。
Eukaryotic Holliday junction (HJ) resolvases have attracted much attention recently with the identification of at least three distinct proteins that can cleave model HJs in vitro. However, the specificDNAstructure(s) that these proteins act upon in the cell is unknown. Here, we describe a system in budding yeast to directly and quantitatively monitor in vivo HJ resolution. We found that Yen1 acts redundantly with Mus81, but not Slx1, to resolve a model HJ in vivo. This functional overlap specifically extends to the repair/bypass of lesions that impede the progression of replication forks but not to the repair of double-strand breaks induced by ionizing radiation. Together, these results suggest a direct role for Yen1 in the response to DNA damage and implicate overlapping HJ resolution functions of Yen1 with Mus81 during replication fork repair.