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

作者：Congling Xu, Chengyu Li, Jiwei Chen, Yan Xiong, Zhibin Qiao, Pengyu Fan, Conghui Li, Shuangyu Ma, Jin Liu, Aixia Song, Bolin Tao, Tao Xu, Wei Xu, Yayun Chi, Jingyan Xue, Pu Wang, Dan Ye, Hongzhou Gu, Peng Zhang, Qiong Wang, R. Xiao, Jingdong Cheng, Hai Zheng, Xiaoli Yu, Zhen Zhang, Jiong Wu, Kaiwei Liang, Yanjun Liu, Huasong Lu, Fei Chen · 发表于：Nature · 年份：2023 · DOI：10.1038/s41586-023-06515-5 · 被引用次数：108 · 研究领域：DNA Repair Mechanisms、Genomics and Chromatin Dynamics、CRISPR and Genetic Engineering

Abstract 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.