一个监控机制确保DNA损伤在zygotic重编程
Sabrina Ladstätter1, Kikuë Tachibana-Konwalski1
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter, Dr. Bohr-Gasse 3, Vienna 1030, Austria.
Cell
|December 6, 2016
概括
在脱甲基化过程中产生父性DNA损伤. 监测机制修复这些病变以防止线粒延迟,胚胎丧失和不孕.
科学领域:
- 生殖生物学
- 表观遗传学
- DNA 修复
背景情况:
- 性繁殖需要胚胎全能,通过精子染色质重组和表观遗传重编程实现.
- 父亲基因组去甲基化涉及DNA修复,但导致的DNA损伤及其后果尚不清楚.
研究的目的:
- 调查胚胎重编程过程中的DNA损伤的性质和后果.
- 确定监测和修复这些病变的机制.
主要方法:
- 使用了小鼠遗传学和化学生物学方法.
- 为了研究DNA修复,使用了体内结构功能救援试验.
- 分析了检查点的激活及其对线粒体进入的影响.
主要成果:
- 这种重编程会产生父性DNA损伤.
- 一个监控机制监测这些DNA损伤.
- 这种依赖于凝聚素的病变修复可以防止依赖于Chk1的检查点的激活,从而避免线粒延迟.
- 培养条件影响检查点的严格性.
结论:
- 细胞检查点检测出来自父DNA脱甲基的DNA损伤.
- 这些病变的修复对于防止染色体碎片化,胚胎丧失和不孕症至关重要.
- 这些发现对人类体外受精结果有影响.
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