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Peer-reviewedCC BY 4.0Nucleic Acids Research

The 7SK small nuclear ribonucleoprotein links the cell responses to transcription and replication stress by promoting replication fork reversal and homologous recombination

  • Akhil Bowry1,2
  • Claire Wilson3
  • Richard D W Kelly1,2
  • Rosanna J Wilkins1,2
  • Alexandra K Walker1,2
  • Christy S Varghese1,2
  • Zahraa A M Alshatti1,2
  • Siobhan Murphy-Hollies1,2
  • Joanna R Morris1,2
  • Sylvain Egloff4
  • Aditi Kanhere3,5
  • Eva Petermann1,2
5 affiliations
  1. 1Department of Cancer and Genomic Sciences, School of Medical Sciences, College of Medicine and Health, University of Birmingham , Birmingham B15 2TT ,
  2. 2Birmingham Centre for Genome Biology, University of Birmingham , Birmingham B15 2TT ,
  3. 3Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool , Liverpool L69 7BE ,
  4. 4Centre de Biologie Intégrative de Toulouse, University of Toulouse, CNRS, CBI , Toulouse 31400 ,
  5. 5Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool , Liverpool L69 7BE ,
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Abstract

The 7SK small nuclear ribonucleoprotein (7SK-snRNP) releases positive transcription elongation factor b to sustain RNA polymerase II (RNAPII) activity during transcription stress. Many conditions that block transcription also cause replication stress, and 7SK-snRNP components have potential roles in transcription–replication conflicts and double-strand break (DSB) repair. Here, we investigate roles of 7SK-snRNP components in replication stress responses. We report that 7SK-snRNP promotes replication fork slowing in response to agents that cause both replication and transcription stress. Our data suggest that 7SK-snRNP facilitates RAD51-mediated replication fork reversal rather than transcription–replication conflicts. 7SK-snRNP also promotes RAD51 recruitment to replication-associated DSBs or post-replicative gaps under conditions of transcription stress and supports homologous recombination at direct DSBs. In contrast, 7SK-snRNP components are not required for RAD51 recruitment in response to hydroxyurea. Our data support that LARP7 functions during replication stress independently of its interaction with BRCA1, and that LARP7 and HEXIM1 promote survival of replication stress. 7SK-snRNP components are not recruited to stressed replication forks, and RNAPII inhibition phenocopies loss of these proteins. Our data support a model where 7SK-snRNP modulation of RNAPII activity helps facilitate several RAD51 functions under transcription stress conditions, thereby connecting the cell responses to transcription and replication stress.

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Cite

BibTeXRIS
BibTeX
@article{bowry2026small,
  title = {{The 7SK small nuclear ribonucleoprotein links the cell responses to transcription and replication stress by promoting replication fork reversal and homologous recombination}},
  author = {Akhil Bowry and Claire Wilson and Richard D W Kelly and Rosanna J Wilkins and Alexandra K Walker and Christy S Varghese and Zahraa A M Alshatti and Siobhan Murphy-Hollies and Joanna R Morris and Sylvain Egloff and Aditi Kanhere and Eva Petermann},
  journal = {Nucleic Acids Research},
  year = {2026},
  month = oct,
  doi = {10.1093/nar/gkag1021},
  url = {https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1021/9004257},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The 7SK small nuclear ribonucleoprotein links the cell responses to transcription and replication stress by promoting replication fork reversal and homologous recombination
AU  - Akhil Bowry
AU  - Claire Wilson
AU  - Richard D W Kelly
AU  - Rosanna J Wilkins
AU  - Alexandra K Walker
AU  - Christy S Varghese
AU  - Zahraa A M Alshatti
AU  - Siobhan Murphy-Hollies
AU  - Joanna R Morris
AU  - Sylvain Egloff
AU  - Aditi Kanhere
AU  - Eva Petermann
PY  - 2026
DA  - 2026/10/01
JO  - Nucleic Acids Research
DO  - 10.1093/nar/gkag1021
UR  - https://academic.oup.com/nar/article/doi/10.1093/nar/gkag1021/9004257
AB  - The 7SK small nuclear ribonucleoprotein (7SK-snRNP) releases positive transcription elongation factor b to sustain RNA polymerase II (RNAPII) activity during transcription stress. Many conditions that block transcription also cause replication stress, and 7SK-snRNP components have potential roles in transcription–replication conflicts and double-strand break (DSB) repair. Here, we investigate roles of 7SK-snRNP components in replication stress responses. We report that 7SK-snRNP promotes replication fork slowing in response to agents that cause both replication and transcription stress. Our data suggest that 7SK-snRNP facilitates RAD51-mediated replication fork reversal rather than transcription–replication conflicts. 7SK-snRNP also promotes RAD51 recruitment to replication-associated DSBs or post-replicative gaps under conditions of transcription stress and supports homologous recombination at direct DSBs. In contrast, 7SK-snRNP components are not required for RAD51 recruitment in response to hydroxyurea. Our data support that LARP7 functions during replication stress independently of its interaction with BRCA1, and that LARP7 and HEXIM1 promote survival of replication stress. 7SK-snRNP components are not recruited to stressed replication forks, and RNAPII inhibition phenocopies loss of these proteins. Our data support a model where 7SK-snRNP modulation of RNAPII activity helps facilitate several RAD51 functions under transcription stress conditions, thereby connecting the cell responses to transcription and replication stress.
SN  - 0305-1048
SN  - 1362-4962
ER  -