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Coordination of transcription-coupled repair and repair-independent release of lesion-stalled RNA polymerase II

Author

Listed:
  • Yongchang Zhu

    (Fudan University)

  • Xiping Zhang

    (Fudan University)

  • Meng Gao

    (Fudan University)

  • Yanchao Huang

    (Fudan University)

  • Yuanqing Tan

    (Fudan University)

  • Avital Parnas

    (The Hebrew University of Jerusalem)

  • Sizhong Wu

    (Fudan University)

  • Delin Zhan

    (Fudan University)

  • Sheera Adar

    (The Hebrew University of Jerusalem)

  • Jinchuan Hu

    (Fudan University)

Abstract

Transcription-blocking lesions (TBLs) stall elongating RNA polymerase II (Pol II), which then initiates transcription-coupled repair (TCR) to remove TBLs and allow transcription recovery. In the absence of TCR, eviction of lesion-stalled Pol II is required for alternative pathways to address the damage, but the mechanism is unclear. Using Protein-Associated DNA Damage Sequencing (PADD-seq), this study reveals that the p97-proteasome pathway can evict lesion-stalled Pol II independently of repair. Both TCR and repair-independent eviction require CSA and ubiquitination. However, p97 is dispensable for TCR and Pol II eviction in TCR-proficient cells, highlighting repair’s prioritization over repair-independent eviction. Moreover, ubiquitination of RPB1-K1268 is important for both pathways, with USP7’s deubiquitinase activity promoting TCR without abolishing repair-independent Pol II release. In summary, this study elucidates the fate of lesion-stalled Pol II, and may shed light on the molecular basis of genetic diseases caused by the defects of TCR genes.

Suggested Citation

  • Yongchang Zhu & Xiping Zhang & Meng Gao & Yanchao Huang & Yuanqing Tan & Avital Parnas & Sizhong Wu & Delin Zhan & Sheera Adar & Jinchuan Hu, 2024. "Coordination of transcription-coupled repair and repair-independent release of lesion-stalled RNA polymerase II," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51463-x
    DOI: 10.1038/s41467-024-51463-x
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