文章基本信息

标题：Physical proximity of chromatin to nuclear pores prevents harmful R loop accumulation contributing to maintain genome stability
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作者：Francisco García-Benítez ; Hélène Gaillard ; Andrés Aguilera 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：41
页码：10942-10947
DOI：10.1073/pnas.1707845114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：During transcription, the mRNA may hybridize with DNA, forming an R loop, which can be physiological or pathological, constituting in this case a source of genomic instability. To understand the mechanism by which eukaryotic cells prevent harmful R loops, we used human activation-induced cytidine deaminase (AID) to identify genes preventing R loops. A screening of 400 Saccharomyces cerevisiae selected strains deleted in nuclear genes revealed that cells lacking the Mlp1/2 nuclear basket proteins show AID-dependent genomic instability and replication defects that were suppressed by RNase H1 overexpression. Importantly, DNA–RNA hybrids accumulated at transcribed genes in mlp1/2 mutants, indicating that Mlp1/2 prevents R loops. Consistent with the Mlp1/2 role in gene gating to nuclear pores, artificial tethering to the nuclear periphery of a transcribed locus suppressed R loops in mlp1 ∆ cells. The same occurred in THO-deficient hpr1 ∆ cells. We conclude that proximity of transcribed chromatin to the nuclear pore helps restrain pathological R loops.
关键词：nuclear pores ; transcription ; R loop ; genome instability ; Mpl1/2