| HRA009292
(Open Access)
|
In this study, we identify the Integrator complex as a critical mediator of Pol II removal to ensure efficient TC-NER. INTS12, a flexible subunit of the Integrator complex with previously uncharacterized functions, is rapidly phosphorylated in response to UV irradiation.This phosphorylation enhances INTS12 interaction with CSB, promoting the recruitment of the Integrator complex to facilitate the release of lesion-stalled Pol II and subsequent DNA repair. Disruption of this INTS12-mediated pathway impairs transcription recovery and TC-NER, leading to reduced cellular resistance to UV-induced stress. Interestingly, the INTS12-coordinated removal of stalled Pol II is less favorable for transcription-coupled DNA-protein crosslink (TC-DPC) repair, which relies on proteolytic degradation of stalled Pol II for DPC removal. |
