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端粒长度决定了细胞循环中的TERRA和R循环调节

Marco Graf¹, Diego Bonetti¹, Arianna Lockhart¹

¹Institute of Molecular Biology (IMB), 55128 Mainz, Germany.

|July 1, 2017

概括

由于RNA降解受损,短端粒通过积累TERRARNA-DNA杂交 (R环) 来触发同质导向修复 (HDR). 这一过程对于防止细胞衰老至关重要.

科学领域:

分子生物学
遗传学
细胞生物学

背景情况:

保持端粒长度对于防止细胞衰老至关重要.
在缺少端粒酶的情况下,同质导向修复 (HDR) 修复了极短的端粒,防止过早衰老.
对于HDR最短端粒的具体向仍然不清楚.

研究的目的:

调查最短端粒优先针对同质导向修复 (HDR) 的机制.
阐明非编码RNATERRA和RNA-DNA混合体 (R-循环) 在这个过程中的作用.
了解TERRA降解的调节及其对端粒复制和衰老的影响.

主要方法:

在不同长度的端粒中分析TERRA积累.
研究涉及Rat1和RNase H2核酶的RNA降解途径.
对DNA损伤反应 (DDR) 激活和Rad51重组酶的评估.

主要成果:

特别是在非常短的端粒中,TERRA以促进HDR的RNA- DNA混合体 (R- 环) 的形式积累.
通过Rat1和RNase H2核酶降解RNA的局部缺陷导致缩短的端粒的TERRA和R循环增加.
在缩短的端粒中,TERRA降解与端粒复制的改变导致了R循环的持续性.

结论:

对TERA及其R循环的端粒长度依赖调节对于HDR准至关重要.
在短端粒处持续存在的R环激活了DNA损伤反应 (DDR) 并促进了Rad51的招募.
这种机制决定了复制衰老的速度.

关键词:

德意志民主共和国在 R 循环一个RNA-DNA混合体 RNase H2 的使用情况一个老鼠.在Rif2 美国年老长质子

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