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拓扑异构酶I可防止转录终止位点处的转录-复制冲突。

Topoisomerase I prevents transcription-replication conflicts at transcription termination sites.

作者信息

Liu Yaqun, Lin Yea-Lih, Pasero Philippe, Chen Chun-Long

机构信息

Institut Curie, PSL Research University, CNRS, UMR3244, Sorbonne Université, Paris, France.

Institut de Génétique Humaine, CNRS et Université de Montpellier, Montpellier, France.

出版信息

Mol Cell Oncol. 2020 Dec 7;8(1):1843951. doi: 10.1080/23723556.2020.1843951.

DOI:10.1080/23723556.2020.1843951
PMID:33553603
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7849740/
Abstract

R-loops have both positive and negative impacts on chromosome functions. To identify toxic R-loops, we mapped RNA:DNA hybrids, markers of replication fork stalling and DNA double-strand breaks along the human genome. This analysis indicates that transient replication fork pausing occurs at the transcription termination sites of highly expressed genes enriched in R-loops and prevents head-on conflicts with transcription, in a topoisomerase I-dependent manner.

摘要

R环对染色体功能既有积极影响,也有消极影响。为了识别有害的R环,我们绘制了RNA:DNA杂交体、复制叉停滞标记以及人类基因组中的DNA双链断裂图谱。该分析表明,短暂的复制叉暂停发生在富含R环的高表达基因的转录终止位点,并以拓扑异构酶I依赖的方式防止与转录发生迎头冲突。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d68f/7849740/5fadbf621ef3/KMCO_A_1843951_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d68f/7849740/5fadbf621ef3/KMCO_A_1843951_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d68f/7849740/5fadbf621ef3/KMCO_A_1843951_F0001_OC.jpg

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本文引用的文献

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Nat Commun. 2020 Aug 7;11(1):3940. doi: 10.1038/s41467-020-17858-2.
2
Regulatory R-loops as facilitators of gene expression and genome stability.调控性 R 环作为基因表达和基因组稳定性的促进因子。
Nat Rev Mol Cell Biol. 2020 Mar;21(3):167-178. doi: 10.1038/s41580-019-0206-3. Epub 2020 Jan 31.
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Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses.
细胞自主和非自主过程都调节复制时间和突变率之间的关联。
Sci Rep. 2023 Aug 12;13(1):13143. doi: 10.1038/s41598-023-39463-1.
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OKseqHMM: a genome-wide replication fork directionality analysis toolkit.OKseqHMM:一个全基因组复制叉方向分析工具包。
Nucleic Acids Res. 2023 Feb 28;51(4):e22. doi: 10.1093/nar/gkac1239.
5
Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship.复制压力、基因组不稳定性和复制时间:复杂的关系。
Int J Mol Sci. 2021 Apr 30;22(9):4764. doi: 10.3390/ijms22094764.
转录-复制冲突方向调节R环水平并激活不同的DNA损伤反应。
Cell. 2017 Aug 10;170(4):774-786.e19. doi: 10.1016/j.cell.2017.07.043.
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Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage.共转录R环是雌激素诱导DNA损伤的主要原因。
Elife. 2016 Aug 23;5:e17548. doi: 10.7554/eLife.17548.
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Prevalent, Dynamic, and Conserved R-Loop Structures Associate with Specific Epigenomic Signatures in Mammals.普遍存在、动态变化且保守的R环结构与哺乳动物特定的表观基因组特征相关。
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Genes Dev. 2016 Feb 1;30(3):337-54. doi: 10.1101/gad.273813.115. Epub 2016 Jan 21.
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