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Coordination of transcription-coupled repair and repair-independent release of lesion-stalled RNA polymerase II.
- Source :
-
Nature communications [Nat Commun] 2024 Aug 17; Vol. 15 (1), pp. 7089. Date of Electronic Publication: 2024 Aug 17. - Publication Year :
- 2024
-
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.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Ubiquitin-Specific Peptidase 7 metabolism
Ubiquitin-Specific Peptidase 7 genetics
Valosin Containing Protein metabolism
Valosin Containing Protein genetics
Proteasome Endopeptidase Complex metabolism
Excision Repair
RNA Polymerase II metabolism
DNA Repair
Ubiquitination
Transcription, Genetic
DNA Damage
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39154022
- Full Text :
- https://doi.org/10.1038/s41467-024-51463-x