Stepwise transcription stalling by the anti-cancer drug Actinomycin D and insights into short tandem repeat transcription inhibition - PubMed
6 hours ago
- #short tandem repeats
- #Actinomycin D
- #transcription inhibition
- Actinomycin D (ACTD) is an anti-cancer drug that inhibits transcription, but its mechanism is not fully understood.
- The study investigates ACTD's impact on transcription, particularly on short tandem repeats (STRs), which are linked to over 60 diseases.
- ACTD induces RNA polymerase II (Pol II) pausing at three distinct states, and structural snapshots of Pol II processing ACTD are presented.
- The research examines ACTD's effects on Pol II transcribing five disease-linked, GC-rich STRs, including CTG repeats associated with myotonic dystrophy type 1.
- Findings reveal the structural basis of ACTD-mediated transcription inhibition and suggest a framework for modifying ACTD to target STR-associated disorders.