Wang, Zihao, Zhang, Yizheng, Guo, Ting, He, Ming, Xu, Yingying, Bhattacharjee, Sonali, Martienssen, Robert A, Ren, Jie (October 2025) Dcr1 senses R-loops for RNAPII termination at sites of replication stress and repair pathway choice. Molecular Cell. ISSN 1097-2765 (Public Dataset)
Abstract
Stalled RNA polymerase II (RNAPII) threatens genome integrity, yet how cells resolve transcription blocks at difficult-to-terminate sites is unclear. Leveraging the compact genome of fission yeast and termination defects associated with the non-canonical function of Dcr1, we unravel the recognition and release mechanisms of stalled RNAPII. Through dual recognition, Dcr1 senses the difficult-to-terminate context-stalled RNAPII and accumulated R-loops-and recruits the termination factor Dhp1 to ensure efficient RNAPII release. Failure of this mechanism causes termination defects that impede replication forks, necessitating DNA polymerase delta (DNAPδ)-mediated replication fork restart at stalled sites. Moreover, Dcr1 promotes genome stability by repurposing its hybrid-recognition ability to engage Rad51, thereby biasing DNA repair toward high-fidelity homologous recombination. Our work defines a key chromatin context and mechanisms governing RNAPII termination, establishing Dcr1 as a molecular hub that directly couples the fidelity of transcription termination to the stability of the genome during replication and repair.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA repair |
| CSHL Authors: | |
| Communities: | CSHL labs > Martienssen lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 28 October 2025 |
| Date Deposited: | 03 Nov 2025 13:46 |
| Last Modified: | 03 Nov 2025 13:46 |
| Related URLs: | |
| Dataset ID: |
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| URI: | https://repository.cshl.edu/id/eprint/42000 |
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