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

Author

Listed:
  • Congling Xu

    (Fudan University)

  • Chengyu Li

    (Zhejiang University)

  • Jiwei Chen

    (Fudan University)

  • Yan Xiong

    (Fudan University)

  • Zhibin Qiao

    (Fudan University
    Fudan University Shanghai Cancer Center, Fudan University)

  • Pengyu Fan

    (Fudan University
    Tongji University School of Medicine)

  • Conghui Li

    (Wuhan University)

  • Shuangyu Ma

    (Shanghai Jiao Tong University School of Medicine)

  • Jin Liu

    (Fudan University)

  • Aixia Song

    (Fudan University)

  • Bolin Tao

    (Fudan University)

  • Tao Xu

    (Anhui Medical University)

  • Wei Xu

    (Second Military Medical University)

  • Yayun Chi

    (Fudan University Shanghai Cancer Center)

  • Jingyan Xue

    (Fudan University Shanghai Cancer Center)

  • Pu Wang

    (Shanghai Medical College of Fudan University)

  • Dan Ye

    (Shanghai Medical College of Fudan University)

  • Hongzhou Gu

    (Fudan University)

  • Peng Zhang

    (Tongji University School of Medicine)

  • Qiong Wang

    (Shanghai Jiao Tong University School of Medicine)

  • Ruijing Xiao

    (Wuhan University)

  • Jingdong Cheng

    (Fudan University)

  • Hai Zheng

    (Fudan University)

  • Xiaoli Yu

    (Fudan University Shanghai Cancer Center, Fudan University)

  • Zhen Zhang

    (Fudan University Shanghai Cancer Center, Fudan University)

  • Jiong Wu

    (Fudan University Shanghai Cancer Center)

  • Kaiwei Liang

    (Wuhan University)

  • Yan-Jun Liu

    (Fudan University)

  • Huasong Lu

    (Zhejiang University)

  • Fei Xavier Chen

    (Fudan University
    Fudan University Shanghai Cancer Center, Fudan University)

Abstract

The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. 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.

Suggested Citation

  • 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 Y, 2023. "R-loop-dependent promoter-proximal termination ensures genome stability," Nature, Nature, vol. 621(7979), pages 610-619, September.
    • Handle: RePEc:nat:nature:v:621:y:2023:i:7979:d:10.1038_s41586-023-06515-5
    DOI: 10.1038/s41586-023-06515-5
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    Cited by:

    1. Ruitu Lyu & Yun Gao & Tong Wu & Chang Ye & Pingluan Wang & Chuan He, 2024. "Quantitative analysis of cis-regulatory elements in transcription with KAS-ATAC-seq," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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