生物
RNA剪接
基因组不稳定性
核糖核酸酶P
分子生物学
体细胞突变
核糖核酸
DNA
核糖核酸酶H
基因
抄写(语言学)
遗传学
细胞生物学
DNA损伤
B细胞
抗体
哲学
语言学
作者
Xialu Li,James L. Manley
出处
期刊:Cell
[Elsevier]
日期:2005-08-01
卷期号:122 (3): 365-378
被引量:670
标识
DOI:10.1016/j.cell.2005.06.008
摘要
SR proteins constitute a family of pre-mRNA splicing factors now thought to play several roles in mRNA metabolism in metazoan cells. Here we provide evidence that a prototypical SR protein, ASF/SF2, is unexpectedly required for maintenance of genomic stability. We first show that in vivo depletion of ASF/SF2 results in a hypermutation phenotype likely due to DNA rearrangements, reflected in the rapid appearance of DNA double-strand breaks and high-molecular-weight DNA fragments. Analysis of DNA from ASF/SF2-depleted cells revealed that the nontemplate strand of a transcribed gene was single stranded due to formation of an RNA:DNA hybrid, R loop structure. Stable overexpression of RNase H suppressed the DNA-fragmentation and hypermutation phenotypes. Indicative of a direct role, ASF/SF2 prevented R loop formation in a reconstituted in vitro transcription reaction. Our results support a model by which recruitment of ASF/SF2 to nascent transcripts by RNA polymerase II prevents formation of mutagenic R loop structures.
科研通智能强力驱动
Strongly Powered by AbleSci AI