Transcription termination counteracts DNA damage after WEE1 inhibition.

ABSTRACT: Transcription termination is a key regulatory step in transcription and a potential target for cancer therapy, but how it can be exploited for treatment is incompletely understood. Here we show that transcription termination plays a crucial role in mitigating DNA damage and cell death upon WEE1 inhibition by adavosertib. Depleting five different transcription termination factors (WDR82, PNUTS, XRN2, DDX5, or CPSF73) increased adavosertib-induced DNA damage in S-phase. Conversely, inhibiting active transcription with DRB or triptolide, or co-depleting CDC73, a component of the PAF1 transcription elongation complex, reduced such damage. Additionally, read-through transcription following WDR82 depletion was partially inhibited by co-depletion of CDC73, supporting that read-through transcripti

SUBMITTER: Landsverk HB 

PROVIDER: S-EPMC12825307 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature