Back to Search
Start Over
R-loop-dependent promoter-proximal termination ensures genome stability
- Source :
- Nature; 20230101, Issue: Preprints p1-10, 10p
- Publication Year :
- 2023
-
Abstract
- The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)3and the transcription regulator Integrator-PP2A (INTAC)4–6. Through SSB1-mediated recognition of single-stranded DNA, SOSS–INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS–INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2(encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS–INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.
Details
- Language :
- English
- ISSN :
- 00280836 and 14764687
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Nature
- Publication Type :
- Periodical
- Accession number :
- ejs63900437
- Full Text :
- https://doi.org/10.1038/s41586-023-06515-5