在整个细胞周期中,CTIP-BRCA1调节了DNA双链断裂修复途径的选择
1Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
Nature
|April 10, 2009
概括
CtIP蛋白作为细胞周期开关,指导DNA双链断裂的修复. 它在血清327的酸化促进了S/G2的无错同源重组,而MMEJ在G1中占主导地位.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 在整个细胞周期中,通过不同的途径修复DNA双链断裂 (DSB).
- 非同源端连接 (NHEJ) 和微同源介导端连接 (MMEJ) 是G1中普遍存在的易出错的路径.
- 同源重组 (HR) 是在S/G2阶段受青的无误路径.
研究的目的:
- 阐明控制DSB不同DNA修复途径之间的选择机制.
- 确定CtIP (RBBP8) 在细胞周期期间指导DSB修复路径选择中的作用.
主要方法:
- 使用了鸟类B细胞系DT40.
- 研究了CtIP在DSB修复通路中的功能.
- 分析了CtIP血清327酸化和BRCA1招募对修复忠实性的影响.
主要成果:
- 对于G1中的MMEJ和S/G2中的HR,CtIP对于G1中的MMEJ和HR都至关重要.
- CtIP的HR功能,但不是MMEJ,取决于血清蛋白327酸化和BRCA1招募.
- 突变CtIP缺乏氨酸327酸化会损害HR,并在损伤后减少单链DNA,而MMEJ不受影响.
结论:
- 在血清327中CtIP的酸化起到细胞周期依赖的分子开关的作用.
- 这种开关,与BRCA1招募一起,将DSB修复从易出错的末端连接转变为无错同类重组.
- 通过调节DSB修复路径选择,CTIP在维护基因组完整性方面发挥着至关重要的作用.
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