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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, 09/2023, Letnik: 621, Številka: 7979Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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