The MluI cell cycle box (MCB) motifs, but not damage-responsive elements (DREs), are responsible for the transcriptional induction of the rhp51+ gene in response to DNA replication stress.
The MluI cell cycle box (MCB) motifs, but not damage-responsive elements (DREs), are responsible for the transcriptional induction of the rhp51+ gene in response to DNA replication stress.
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DOI：
10.1371/journal.pone.0111936
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ma Y
中科院分区：
文献类型：
--
作者：
Sartagul W;Zhou X;Yamada Y;Ma N;Tanaka K;Furuyashiki T;Ma Y
DNA 复制应激诱导 rhp51 + 的转录激活，rhp51 + 是修复 DNA 双链断裂所需的裂殖酵母 recA 同源物。然而，DNA 复制应激激活 rhp51 + 转录的机制尚不清楚。 rhp51 + 的启动子区域包含两个损伤响应元件 (DRE) 和两个 MluI 细胞周期盒 (MCB) 基序。使用荧光素酶报告基因检测，我们检查了这些元件在 rhp51 + 转录中的作用。全长 rhp51 + 启动子和仅包含 MCB 基序的启动子片段（但不包含 DRE 的片段）在 DNA 复制应激时介导转录激活。从 rhp51 + 启动子中去除 MCB 基序消除了 DNA 复制应激对 rhp51 + 转录的诱导。与 MCB 基序在 rhp51 + 转录激活中的作用一致，MBF（MCB 结合因子）辅阻遏物 Nrm1 和 Yox1 的缺失阻止了 rhp51 + 转录诱导以响应 DNA 复制应激。使用缺乏检查点信号分子的细胞，我们发现 Rad3-Cds1/Chk1 通路部分介导 rhp51 + 转录以响应 DNA 复制应激，这表明存在未识别的检查点信号通路。由于 MBF 对于 G1/S 转录至关重要，因此我们研究了细胞周期如何影响 rhp51 + 转录。 rhp51 + 和 cdc18 +（MBF 依赖性 G1/S 基因）的转录在同步的 cdc25-22 细胞中同时达到峰值。此外，与 cdc18 + 类似，DNA 复制应激维持 rhp51 + 的转录。总的来说，这些结果表明 MBF 及其调节因子介导 rhp51 + 转录以响应 DNA 复制应激，并且是 G1/S 转变时 rhp51 + 转录的基础。
DNA replication stress induces the transcriptional activation of rhp51 +, a fission yeast recA homolog required for repair of DNA double strand breaks. However, the mechanism by which DNA replication stress activates rhp51 + transcription is not understood. The promoter region of rhp51 + contains two damage-responsive elements (DREs) and two MluI cell cycle box (MCB) motifs. Using luciferase reporter assays, we examined the role of these elements in rhp51 + transcription. The full-length rhp51 + promoter and a promoter fragment containing MCB motifs only, but not a fragment containing DREs, mediated transcriptional activation upon DNA replication stress. Removal of the MCB motifs from the rhp51 + promoter abolished the induction of rhp51 + transcription by DNA replication stress. Consistent with a role for MCB motifs in rhp51 + transcription activation, deletion of the MBF (MCB-binding factor) co-repressors Nrm1 and Yox1 precluded rhp51 + transcriptional induction in response to DNA replication stress. Using cells deficient in checkpoint signaling molecules, we found that the Rad3-Cds1/Chk1 pathway partially mediated rhp51 + transcription in response to DNA replication stress, suggesting the involvement of unidentified checkpoint signaling pathways. Because MBF is critical for G1/S transcription, we examined how the cell cycle affected rhp51 + transcription. The transcription of rhp51 + and cdc18 +, an MBF-dependent G1/S gene, peaked simultaneously in synchronized cdc25-22 cells. Furthermore, DNA replication stress maintained transcription of rhp51 + similarly to cdc18 +. Collectively, these results suggest that MBF and its regulators mediate rhp51 + transcription in response to DNA replication stress, and underlie rhp51 + transcription at the G1/S transition.
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影响因子：
3.7
作者：
Caetano, Catia;Klier, Steffi;de Bruin, Robertus A. M.
通讯作者：
de Bruin, Robertus A. M.
影响因子：
16
作者：
de Bruin, Robertus A. M.;Kalashnikova, Tatyana I.;Wittenberg, Curt
通讯作者：
Wittenberg, Curt
影响因子：
5.3
作者：
Dutta, Chaitali;Patel, Prasanta K.;Rhind, Nicholas
通讯作者：
Rhind, Nicholas
影响因子：
3.3
作者：
Gaits, F;Russell, P
通讯作者：
Russell, P
影响因子：
3.3
作者：
Deng, Lu;Sugiura, Reiko;Kuno, Takayoshi
通讯作者：
Kuno, Takayoshi