Bibliographic Details
| Title: |
Coordination of transcription-coupled repair and repair-independent release of lesion-stalled RNA polymerase II. |
| Authors: |
Zhu, Yongchang, Zhang, Xiping, Gao, Meng, Huang, Yanchao, Tan, Yuanqing, Parnas, Avital, Wu, Sizhong, Zhan, Delin, Adar, Sheera, Hu, Jinchuan |
| Source: |
Nature Communications; 8/21/2024, Vol. 15 Issue 1, p1-15, 15p |
| Subject Terms: |
EXCISION repair, RNA polymerase II, RNA polymerases, GENETIC transcription, DNA damage |
| 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. Transcription-blocking lesions are removed by transcription-coupled repair (TCR). Here the authors show that the p97-proteasome pathway can evict lesion-stalled RNA Pol II independently of repair. However, p97 is dispensable for TCR and Pol II eviction in TCR-proficient cells. [ABSTRACT FROM AUTHOR] |
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| Database: |
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