Resolution of R-loops and transcription-replication conflicts by SETX-BRCA1-BARD1 complex - PubMed
4 hours ago
- #genome integrity
- #transcription-replication conflicts
- #R-loops
- SETX accumulates at transcription pause sites via BRCA1, and the SETX-BRCA1-BARD1 complex resolves R-loops to prevent genome instability.
- BRCA1-BARD1 binds R-loops and enhances SETX-mediated R-loop unwinding, while also counteracting the inhibitory effect of RAD52 on this process.
- Phosphorylation of Ser642 in SETX promotes interaction with BRCA1's BRCT domain; mutations in SETX's catalytic domain or Ser642 cause R-loop accumulation, transcription-replication conflicts, and DNA damage.