R-loop-dependent promoter-proximal termination ensures genome stability

Nature. 2023 Sep;621(7979):610-619. doi: 10.1038/s41586-023-06515-5. Epub 2023 Aug 9.


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)3 and 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.

MeSH terms

  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / metabolism
  • Genome, Human
  • Genomic Instability* / genetics
  • Humans
  • Mutation
  • Promoter Regions, Genetic* / genetics
  • R-Loop Structures* / genetics
  • RNA Polymerase II / metabolism
  • Transcription Termination, Genetic*


  • DNA, Single-Stranded
  • RNA Polymerase II
  • DNA-Binding Proteins