组织素标记H3K36me3通过与MutSα的相互作用来调节人类DNA不匹配的修复
Feng Li1, Guogen Mao, Dan Tong
1Graduate Center for Toxicology, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40506, USA.
Cell
|April 30, 2013
概括
一个表观遗传的组织蛋白标记,H3K36me3,在体内将DNA不匹配修复蛋白招募到染色质中. 这一发现解释了在缺乏MMR基因突变的癌症中微卫星的不稳定性.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
背景情况:
- 修复DNA不匹配 (MMR) 对于复制效率至关重要.
- 人类MMR的体内机制在很大程度上是未知的.
- 微卫星不稳定性 (MSI) 是MMR缺乏的一个标志,经常在癌症中观察到.
研究的目的:
- 为了阐明人体DNA不匹配修复的体内机制.
- 调查表观遗传修饰在MMR招募中的作用.
- 解释在没有可检测的MMR基因突变的癌症中MSI的原因.
主要方法:
- 在体内研究了基因组标记和MMR蛋白之间的相互作用.
- 利用了染色体免疫沉和遗传分析.
- 检查的细胞缺乏SETD2甲基转移酶.
主要成果:
- 表观基因组素标记H3K36me3通过hMSH6 PWWP域直接将hMutSα复合物招募到染色质中.
- 在G1和早期S阶段的H3K36me3丰富确保了DNA复制前的hMutSα存在.
- 缺少SETD2的细胞表现出MSI和增加的突变频率,反映出MMR缺陷的表型.
结论:
- 基斯标记H3K36me3对于在体内招募MMR蛋白质至关重要.
- 这种表观遗传规则为MMR监测提供了一个机制.
- 这项研究解决了MSI在具有野生型MMR基因的癌症中的悖论.
相关概念视频
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01:36Mismatch Repair
Overview
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