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

R-loop-dependent promoter-proximal termination ensures genome stability.
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DOI:
10.1038/s41586-023-06515-5
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发表时间:
2023-09
期刊:
影响因子:
64.8
通讯作者:
Chen, Fei Xavier
Chen, Fei Xavier
中科院分区:
综合性期刊1区
文献类型:
--
作者:
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

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The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS) and the transcription regulator Integrator-PP2A (INTAC). 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. 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.
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