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| Status |
Public on Jun 20, 2023 |
| Title |
R-loop dependent promoter-proximal termination ensures genome stability [PRO-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Precise regulation of transcription is essential to maintain genome integrity, yet key mechanisms coordinating transcription, genome stability and downstream cellular functions remain incomplete. Here we report the identification of SOSS-INTAC, a stable association of the genome stability regulator Sensor of Single-stranded DNA (ssDNA) (SOSS) complex and transcription regulator Integrator-PP2A (INTAC). Via SSB1-mediated ssDNA recognition at its targets, SOSS-INTAC stimulates early termination of transcription and thus attenuates paused Pol II-induced formation of R-loops to prevent its aberrant accumulation that has the risk of increasing chromatin accessibility and compromising genome stability. SOSS-INTAC-mediated attenuation of R-loops is greatly enhanced by SSB1's unique property of forming liquid-like condensates. In contrast, preventing SSB1 condensation through deletion or cancer-associated mutation within its intrinsically disordered region (IDR) leads to pervasive accumulation of R-loops at a genome-wide level. Thus, our study highlights the genomic surveillance function of SOSS-INTAC that enables timely transcriptional termination to constrain aberrant R-loop accumulation and ensure genomic stability.
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| |
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| Overall design |
PRO-seq with 2 biological replicates in DLD-1 cells.
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| |
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| Contributor(s) |
Xu C, Li C, Chen J, Xiong Y, Lu H, Chen FX |
| Citation(s) |
37557913 |
| |
| Submission date |
Jan 29, 2023 |
| Last update date |
Sep 19, 2023 |
| Contact name |
Jiwei Chen |
| E-mail(s) |
chenjiwei124128@126.com
|
| Organization name |
Fudan University
|
| Street address |
130 DongAn Road
|
| City |
Shanghai |
| ZIP/Postal code |
200032 |
| Country |
China |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE223997 |
R-loop dependent promoter-proximal termination ensures genome stability |
|
| Relations |
| BioProject |
PRJNA929277 |
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