Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination
Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination
复制标题
DOI：
10.1016/j.molcel.2007.09.009
复制
发表时间：
2007-10-12
期刊：
影响因子：
16
通讯作者：
Russell, Paul
中科院分区：
文献类型：
--
作者：
Limbo, Oliver;Chahwan, Charly;Russell, Paul
Mre11-Rad50-Nbs1 (MRN) 复合物是 DNA 双链断裂 (DSB) 的主要传感器。招募到 DSB 后，它在催化同源重组 (HR) 修复所需的 5' -> 3' 单链切除中发挥关键作用。未知机制会抑制细胞周期 G1 期的 HR，在此期间非同源末端连接 (NHEJ) 是 DSB 修复的首选模式。在这里，我们描述了裂殖酵母 Ctpl，之所以如此命名是因为它与哺乳动物肿瘤抑制因子 CUP 共享保守结构域。 Ctpl 被招募到 DSB，这对 HR 的修复至关重要。 Ctpl 是有效形成与 DSB 相邻的 RPA 包被的单链 DNA 所必需的，这表明它在 5' -> 31 切除中与 MRN 复合物一起发挥作用。 ctp(1+) 的转录在细胞周期中是周期性的，其表达的开始与 DNA 复制的开始同时发生。这些数据表明 Ctpl 的调节是 HR 细胞周期控制的基础。
The Mre11-Rad50-Nbs1 (MRN) complex is a primary sensor of DNA double-strand breaks (DSBs). Upon recruitment to DSBs, it plays a critical role in catalyzing 5' -> 3' single-strand resection that is required for repair by homologous recombination (HR). Unknown mechanisms repress HR in G1 phase of the cell cycle during which nonhomologous end-joining (NHEJ) is the favored mode of DSB repair. Here we describe fission yeast Ctpl, so-named because it shares conserved domains with the mammalian tumor suppressor CUP. Ctpl is recruited to DSBs where it is essential for repair by HR. Ctpl is required for efficient formation of RPA-coated single-strand DNA adjacent to DSBs, indicating that it functions with the MRN complex in 5' -> 31 resection. Transcription of ctp(1+) is periodic during the cell cycle, with the onset of its expression coinciding with the start of DNA replication. These data suggest that regulation of Ctpl underlies cell-cycle control of HR.