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R-loop-dependent promoter-proximal termination ensures genome stability

The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions(1,2). Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)(3) and the transcription regulator Integrator...

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Autores principales: Xu, Congling, Li, Chengyu, Chen, Jiwei, Xiong, Yan, Qiao, Zhibin, Fan, Pengyu, Li, Conghui, Ma, Shuangyu, Liu, Jin, Song, Aixia, Tao, Bolin, Xu, Tao, Xu, Wei, Chi, Yayun, Xue, Jingyan, Wang, Pu, Ye, Dan, Gu, Hongzhou, Zhang, Peng, Wang, Qiong, Xiao, Ruijing, Cheng, Jingdong, Zheng, Hai, Yu, Xiaoli, Zhang, Zhen, Wu, Jiong, Liang, Kaiwei, Liu, Yan-Jun, Lu, Huasong, Chen, Fei Xavier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511320/
https://www.ncbi.nlm.nih.gov/pubmed/37557913
http://dx.doi.org/10.1038/s41586-023-06515-5
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author Xu, Congling
Li, Chengyu
Chen, Jiwei
Xiong, Yan
Qiao, Zhibin
Fan, Pengyu
Li, Conghui
Ma, Shuangyu
Liu, Jin
Song, Aixia
Tao, Bolin
Xu, Tao
Xu, Wei
Chi, Yayun
Xue, Jingyan
Wang, Pu
Ye, Dan
Gu, Hongzhou
Zhang, Peng
Wang, Qiong
Xiao, Ruijing
Cheng, Jingdong
Zheng, Hai
Yu, Xiaoli
Zhang, Zhen
Wu, Jiong
Liang, Kaiwei
Liu, Yan-Jun
Lu, Huasong
Chen, Fei Xavier
author_facet Xu, Congling
Li, Chengyu
Chen, Jiwei
Xiong, Yan
Qiao, Zhibin
Fan, Pengyu
Li, Conghui
Ma, Shuangyu
Liu, Jin
Song, Aixia
Tao, Bolin
Xu, Tao
Xu, Wei
Chi, Yayun
Xue, Jingyan
Wang, Pu
Ye, Dan
Gu, Hongzhou
Zhang, Peng
Wang, Qiong
Xiao, Ruijing
Cheng, Jingdong
Zheng, Hai
Yu, Xiaoli
Zhang, Zhen
Wu, Jiong
Liang, Kaiwei
Liu, Yan-Jun
Lu, Huasong
Chen, Fei Xavier
author_sort Xu, Congling
collection PubMed
description The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions(1,2). Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)(3) and the transcription regulator Integrator-PP2A (INTAC)(4–6). Through SSB1-mediated recognition of single-stranded DNA, SOSS–INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS–INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2 (encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS–INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.
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spelling pubmed-105113202023-09-22 R-loop-dependent promoter-proximal termination ensures genome stability Xu, Congling Li, Chengyu Chen, Jiwei Xiong, Yan Qiao, Zhibin Fan, Pengyu Li, Conghui Ma, Shuangyu Liu, Jin Song, Aixia Tao, Bolin Xu, Tao Xu, Wei Chi, Yayun Xue, Jingyan Wang, Pu Ye, Dan Gu, Hongzhou Zhang, Peng Wang, Qiong Xiao, Ruijing Cheng, Jingdong Zheng, Hai Yu, Xiaoli Zhang, Zhen Wu, Jiong Liang, Kaiwei Liu, Yan-Jun Lu, Huasong Chen, Fei Xavier Nature Article The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions(1,2). Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)(3) and the transcription regulator Integrator-PP2A (INTAC)(4–6). Through SSB1-mediated recognition of single-stranded DNA, SOSS–INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS–INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2 (encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS–INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability. Nature Publishing Group UK 2023-08-09 2023 /pmc/articles/PMC10511320/ /pubmed/37557913 http://dx.doi.org/10.1038/s41586-023-06515-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xu, Congling
Li, Chengyu
Chen, Jiwei
Xiong, Yan
Qiao, Zhibin
Fan, Pengyu
Li, Conghui
Ma, Shuangyu
Liu, Jin
Song, Aixia
Tao, Bolin
Xu, Tao
Xu, Wei
Chi, Yayun
Xue, Jingyan
Wang, Pu
Ye, Dan
Gu, Hongzhou
Zhang, Peng
Wang, Qiong
Xiao, Ruijing
Cheng, Jingdong
Zheng, Hai
Yu, Xiaoli
Zhang, Zhen
Wu, Jiong
Liang, Kaiwei
Liu, Yan-Jun
Lu, Huasong
Chen, Fei Xavier
R-loop-dependent promoter-proximal termination ensures genome stability
title R-loop-dependent promoter-proximal termination ensures genome stability
title_full R-loop-dependent promoter-proximal termination ensures genome stability
title_fullStr R-loop-dependent promoter-proximal termination ensures genome stability
title_full_unstemmed R-loop-dependent promoter-proximal termination ensures genome stability
title_short R-loop-dependent promoter-proximal termination ensures genome stability
title_sort r-loop-dependent promoter-proximal termination ensures genome stability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511320/
https://www.ncbi.nlm.nih.gov/pubmed/37557913
http://dx.doi.org/10.1038/s41586-023-06515-5
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