拓扑异构酶 1 介导的新生前导链 DNA 中核苷酸的去除。
Topoisomerase 1-mediated removal of ribonucleotides from nascent leading-strand DNA.
机构信息
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
出版信息
Mol Cell. 2013 Mar 7;49(5):1010-5. doi: 10.1016/j.molcel.2012.12.021. Epub 2013 Jan 31.
Abstract
RNase H2-dependent ribonucleotide excision repair (RER) removes ribonucleotides incorporated during DNA replication. When RER is defective, ribonucleotides in the nascent leading strand of the yeast genome are associated with replication stress and genome instability. Here, we provide evidence that topoisomerase 1 (Top1) initiates an independent form of repair to remove ribonucleotides from genomic DNA. This Top1-dependent process activates the S phase checkpoint. Deleting TOP1 reverses this checkpoint activation and also relieves replication stress and genome instability in RER-defective cells. The results reveal an additional removal pathway for a very common lesion in DNA, and they imply that the "dirty" DNA ends created when Top1 incises ribonucleotides in DNA are responsible for the adverse consequences of ribonucleotides in RNase H2-defective cells.
摘要
RNASE H2 依赖性核苷酸切除修复（RER）可去除 DNA 复制过程中掺入的核糖核苷酸。当 RER 有缺陷时，酵母基因组新生前导链中的核糖核苷酸与复制应激和基因组不稳定性相关。在这里，我们提供的证据表明拓扑异构酶 1（Top1）启动了一种独立的修复形式，以从基因组 DNA 中去除核糖核苷酸。这种 Top1 依赖性过程激活 S 期检查点。删除 TOP1 可逆转该检查点的激活，并减轻 RER 缺陷细胞中的复制应激和基因组不稳定性。结果揭示了 DNA 中一种非常常见损伤的另一种去除途径，并且它们表明，当 Top1 在 DNA 中切割核糖核苷酸时产生的“脏”DNA 末端是 RNASE H2 缺陷细胞中核糖核苷酸产生不利后果的原因。
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