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核糖核苷酸引发DNA损伤及RNA-DNA损伤反应。

Ribonucleotide triggered DNA damage and RNA-DNA damage responses.

作者信息

Wallace Bret D, Williams R Scott

机构信息

a Genome Integrity and Structural Biology Laboratory; National Institute of Environmental Health Sciences; NIH; DHHS ; Research Triangle Park , NC USA.

出版信息

RNA Biol. 2014;11(11):1340-6. doi: 10.4161/15476286.2014.992283.

DOI:10.4161/15476286.2014.992283
PMID:25692233
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4615641/
Abstract

Research indicates that the transient contamination of DNA with ribonucleotides exceeds all other known types of DNA damage combined. The consequences of ribose incorporation into DNA, and the identity of protein factors operating in this RNA-DNA realm to protect genomic integrity from RNA-triggered events are emerging. Left unrepaired, the presence of ribonucleotides in genomic DNA impacts cellular proliferation and is associated with chromosome instability, gross chromosomal rearrangements, mutagenesis, and production of previously unrecognized forms of ribonucleotide-triggered DNA damage. Here, we highlight recent findings on the nature and structure of DNA damage arising from ribonucleotides in DNA, and the identification of cellular factors acting in an RNA-DNA damage response (RDDR) to counter RNA-triggered DNA damage.

摘要

研究表明,DNA被核糖核苷酸短暂污染的情况超过了所有其他已知类型的DNA损伤之和。核糖掺入DNA的后果,以及在这个RNA-DNA领域中发挥作用以保护基因组完整性免受RNA引发事件影响的蛋白质因子的身份正在逐渐明晰。如果不进行修复,基因组DNA中核糖核苷酸的存在会影响细胞增殖,并与染色体不稳定、染色体大片段重排、诱变以及产生以前未被认识的核糖核苷酸引发的DNA损伤形式有关。在这里,我们重点介绍了关于DNA中核糖核苷酸引起的DNA损伤的性质和结构的最新发现,以及鉴定在RNA-DNA损伤反应(RDDR)中起作用以对抗RNA引发的DNA损伤的细胞因子。

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本文引用的文献

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Ribonuclease H2 in health and disease.健康与疾病中的核糖核酸酶H2
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RNA intrusions change DNA elastic properties and structure.RNA侵入会改变DNA的弹性特性和结构。
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Proteolytic degradation of topoisomerase II (Top2) enables the processing of Top2·DNA and Top2·RNA covalent complexes by tyrosyl-DNA-phosphodiesterase 2 (TDP2).拓扑异构酶 II(Top2)的蛋白水解降解使酪氨酸-DNA-磷酸二酯酶 2(TDP2)能够处理 Top2·DNA 和 Top2·RNA 共价复合物。
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TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function.TDP2 可保护转录免受拓扑异构酶活性的影响,并对正常神经功能至关重要。
Nat Genet. 2014 May;46(5):516-21. doi: 10.1038/ng.2929. Epub 2014 Mar 23.
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Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity.Aprataxin 通过解决腺苷酸化的 RNA-DNA 连接来维持基因组完整性。
Nature. 2014 Feb 6;506(7486):111-5. doi: 10.1038/nature12824. Epub 2013 Dec 22.
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Ribonucleotides are signals for mismatch repair of leading-strand replication errors.核苷酸是前导链复制错误的错配修复的信号。
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