复旦大学陈飞等研究人员合作发现，依赖R环的启动子近端终止确保基因组的稳定性。该研究于2023年8月9日在线发表于国际一流学术期刊《自然》。

研究人员发现SOSS-INTAC是基因组稳定性调控因子单链DNA（ssDNA）传感器（SOSS）和转录调控因子整合因子-PP2A（INTAC）的稳定结合。通过SSB1介导的ssDNA识别，SOSS-INTAC可刺激启动子近端终止转录，并减弱暂停的Pol II相关R环，从而防止R环诱导的基因组不稳定性。SSB1形成液态凝结物的能力增强了SOSS-INTAC对R环的依赖性衰减。

在其内在无序区（IDR）中缺失或引入癌症相关突变会导致R环的普遍积累，这突显了SOSS-INTAC的基因组监控功能，它能及时终止启动子处的转录，从而限制R环的积累，并确保基因组的稳定性。

据悉，转录的适当调控对于维持基因组完整性和执行其他下游细胞功能至关重要。

附：英文原文

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

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

Issue&Volume: 2023-08-09

Abstract: The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here, we identify SOSS-INTAC as a stable association of the genome stability regulator Sensor of Single-stranded DNA (ssDNA) (SOSS)3 and the transcription regulator Integrator-PP2A (INTAC)4-6. Via SSB1-mediated ssDNA recognition, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates paused Pol II-associated R-loops to prevent R-loop-induced genome instability. SOSS-INTAC-dependent attenuation of R-loops is enhanced by SSB1's ability to form liquid-like condensates. Deletion of, or introduction of cancer-associated mutations within its intrinsically disordered region (IDR), leads to 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 to ensure genome stability.

DOI: 10.1038/s41586-023-06515-5

Source: https://www.nature.com/articles/s41586-023-06515-5