In:
Nature, Springer Science and Business Media LLC, Vol. 621, No. 7979 ( 2023-09-21), p. 610-619
Abstract:
The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions 1,2 . 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.
Type of Medium:
Online Resource
ISSN:
0028-0836
,
1476-4687
DOI:
10.1038/s41586-023-06515-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
120714-3
detail.hit.zdb_id:
1413423-8
SSG:
11
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