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Updated: Jul 19, 2025
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Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on TRO Approach
Published on: March 12, 2017
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R-loop-dependent promoter-proximal termination ensures genome stability
Congling Xu1, Chengyu Li2, Jiwei Chen1
1Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, Human Phenome Institute, Fudan University, Shanghai, China.
Nature
|August 9, 2023
Summary
The sensor of single-stranded DNA (SOSS) and Integrator-PP2A (INTAC) complex regulates transcription to maintain genome stability. This complex prevents R-loop accumulation, crucial for preventing DNA damage and ensuring cellular function.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Transcription regulation is vital for genome integrity and cellular functions.
- R-loops, DNA-RNA hybrids, can lead to genome instability if not properly resolved.
Purpose of the Study:
- To identify and characterize the functional association between SOSS and INTAC.
- To elucidate the mechanism by which SOSS-INTAC prevents R-loop accumulation and maintains genome stability.
Main Methods:
- Biochemical assays to confirm the stable association between SOSS and INTAC.
- Analysis of transcription termination and R-loop levels in cells with altered SOSS-INTAC components.
- Investigating the role of SSB1 in SOSS-INTAC function and condensate formation.
Main Results:
- A stable complex of SOSS-INTAC was identified, associating via SSB1 recognition of single-stranded DNA.
- SOSS-INTAC promotes transcription termination at promoters and attenuates R-loops.
- SSB1's ability to form liquid-like condensates enhances R-loop attenuation.
- Loss or mutation of SSB1 leads to widespread R-loop accumulation and genome instability.
Conclusions:
- The SOSS-INTAC complex acts as a genome surveillance mechanism.
- Timely transcription termination at promoters by SOSS-INTAC constrains R-loop accumulation.
- This pathway is essential for maintaining genome stability.
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