Integrator subunit INTS12 links ribotoxic stress to transcription-coupled nucleotide excision repair - PubMed
3 hours ago
- #DNA repair
- #Transcription-coupled repair
- #Genome integrity
- INTS12 links ribotoxic stress response (RSR) to transcription-coupled nucleotide excision repair (TC-NER).
- UV-induced RNA damage triggers RSR, which activates ZAK signaling to phosphorylate INTS12.
- Phosphorylated INTS12 enhances interaction with CSB, recruiting the Integrator complex to lesion-stalled RNA Polymerase II (Pol II).
- This recruitment facilitates Pol II clearance, enabling efficient DNA repair via TC-NER.
- Disruption of INTS12-mediated pathway compromises TC-NER and increases UV sensitivity.
- INTS12's role is context-dependent; it is not beneficial for formaldehyde-induced DNA-protein crosslinks, which rely on proteasome degradation.