RNase H2 roles in genome integrity revealed by unlinking its activities.
RNase H2 roles in genome integrity revealed by unlinking its activities.
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DOI：
10.1093/nar/gkt027
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发表时间：
2013-03-01
影响因子：
14.9
通讯作者：
Cerritelli SM
中科院分区：
文献类型：
--
作者：
Chon H;Sparks JL;Rychlik M;Nowotny M;Burgers PM;Crouch RJ;Cerritelli SM
核糖核酸酶H2(RNase H2)通过分解转录相关的R-环和复制过程中DNA中的核苷酸来保护基因组的完整性。为了解开这两个功能，我们产生了一个酿酒酵母RNaseH2突变体，它可以分解R-环，但不能切割DNA中的单个核苷酸。该突变体明确地将在rnh201Δ菌株中观察到的2-5个碱基缺失与DNA中的单个rNMP相关联。它还在R-环和SGS1介导的复制重新启动之间建立了联系，并识别了由RNaseH2唯一处理的R-环。在小鼠中，任何编码RNaseH2的基因的缺失都会导致胚胎死亡，而在人类中，RNaseH2亚型突变会导致Aicardi-Gtières综合征(AGS)，这是一种神经炎症性疾病。为了确定DNA中的R-环和rNMP在AGS中观察到的缺陷的贡献，我们在酵母中鉴定了一种与AGS相关的突变，该突变在处理这两种底物时受到损害，但具有足够的R-环降解活性，以弥补rnh201ΔSGS1Δ菌株的缺陷。然而，这种与AGS相关的突变累积2-5个碱基缺失的速度与缺失菌株非常相似。
Ribonuclease H2 (RNase H2) protects genome integrity by its dual roles of resolving transcription-related R-loops and ribonucleotides incorporated in DNA during replication. To unlink these two functions, we generated a Saccharomyces cerevisiae RNase H2 mutant that can resolve R-loops but cannot cleave single ribonucleotides in DNA. This mutant definitively correlates the 2–5 bp deletions observed in rnh201Δ strains with single rNMPs in DNA. It also establishes a connection between R-loops and Sgs1-mediated replication reinitiation at stalled forks and identifies R-loops uniquely processed by RNase H2. In mouse, deletion of any of the genes coding for RNase H2 results in embryonic lethality, and in humans, RNase H2 hypomorphic mutations cause Aicardi–Goutières syndrome (AGS), a neuroinflammatory disorder. To determine the contribution of R-loops and rNMP in DNA to the defects observed in AGS, we characterized in yeast an AGS-related mutation, which is impaired in processing both substrates, but has sufficient R-loop degradation activity to complement the defects of rnh201Δ sgs1Δ strains. However, this AGS-related mutation accumulates 2–5 bp deletions at a very similar rate as the deletion strain.
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DOI：
10.1111/j.1742-4658.2009.06909.x
发表时间：
2009-03
期刊：
The FEBS journal
影响因子：
--
作者：
Champoux JJ;Schultz SJ
通讯作者：
Schultz SJ
酿酒酵母中RNase H2损失的转录反应。
影响因子：
3.8
作者：
Arana, Mercedes E.;Kerns, Robnet T.;Wharey, Laura;Gerrish, Kevin E.;Bushel, Pierre R.;Kunkel, Thomas A.
通讯作者：
Kunkel, Thomas A.
影响因子：
64.5
作者：
Li, XL;Manley, JL
通讯作者：
Manley, JL
影响因子：
5.6
作者：
Chon, H;Matsumura, H;Kanaya, S
通讯作者：
Kanaya, S
DOI：
10.1084/jem.20120876
发表时间：
2012-07-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hiller B;Achleitner M;Glage S;Naumann R;Behrendt R;Roers A
通讯作者：
Roers A