气候变化领域集成服务门户(CCPortal): Cotranscriptional R-loop formation by Mfd involves topological partitioning of DNA

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DOI	10.1073/pnas.2019630118
	Cotranscriptional R-loop formation by Mfd involves topological partitioning of DNA
	Portman J.R.; Brouwer G.M.; Bollins J.; Savery N.J.; Strick T.R.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	R-loops are nucleic acid hybrids which form when an RNA invades duplex DNA to pair with its template sequence. Although they are implicated in a growing number of gene regulatory processes, their mechanistic origins remain unclear. We here report real-time observations of cotranscriptional R-loop formation at single-molecule resolution and propose a mechanism for their formation. We show that the bacterial Mfd protein can simultaneously interact with both elongating RNA polymerase and upstream DNA, tethering the two together and partitioning the DNA into distinct supercoiled domains. A highly negatively supercoiled domain forms in between Mfd and RNA polymerase, and compensatory positive supercoiling appears in front of the RNA polymerase and behind Mfd. The nascent RNA invades the negatively supercoiled domain and forms a stable R-loop that can drive mutagenesis. This mechanism theoretically enables any protein that simultaneously binds an actively translocating RNA polymerase and upstream DNA to stimulate R-loop formation. © This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
英文关键词	Magnetic trapping; Mutagenesis; R-loops; Single molecule; Transcription-coupled repair
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179932
作者单位	Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, PSL University, INSERM, CNRS, Paris, 75005, France; Horizons 2020 Innovative Training Network “DNAREPAIRMAN”, Paris, 75005, France; DNA-Protein Interactions Unit, University of Bristol, Bristol, BS8 1TD, United Kingdom; Equipe Labellisée de la Ligue Nationale Contre le Cancer, Paris, 75103, France
推荐引用方式 GB/T 7714	Portman J.R.,Brouwer G.M.,Bollins J.,et al. Cotranscriptional R-loop formation by Mfd involves topological partitioning of DNA[J],2021,118(15).
APA	Portman J.R.,Brouwer G.M.,Bollins J.,Savery N.J.,&Strick T.R..(2021).Cotranscriptional R-loop formation by Mfd involves topological partitioning of DNA.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	Portman J.R.,et al."Cotranscriptional R-loop formation by Mfd involves topological partitioning of DNA".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).