Skip to content
DraconiticResearch
Search Sources API
194,226 studies31 sourcesUpdated 12 min ago
Peer-reviewedCC BY 4.0Nucleic Acids Research

Distinct ways by which Srs2 helicase and Rrp1 translocase shape Rad51–DNA interactions in fission yeast

  • Dorota Misiorna1
  • Dorota Dziadkowiec1
  • Karol Kramarz2
  1. 1Department of Biotransformation, Faculty of Biotechnology, University of Wrocław , Wrocław 50-383 ,
  2. 2Department of Genetics and Cell Physiology, Faculty of Biological Sciences, University of Wrocław , Wrocław 50-328 ,
Open at sourcePDFDOICite

Abstract

Precise regulation of homologous recombination is essential for genome stability. Multiple helicases and translocases prevent toxic, unscheduled association of the Rad51 recombinase with chromatin, and their levels are frequently dysregulated in cancer. It remains unclear how anti-recombinogenic enzymes act on distinct pools of Rad51. Using Schizosaccharomyces pombe, we show that the Srs2 helicase and Rrp1 translocase may target distinct Rad51 species through recombinase substrate specificity and activity control. Genetic analyses support a model in which Srs2 may preferentially regulate Rad52-dependent Rad51 nucleofilaments associated with single-stranded DNA (ssDNA), whereas Rrp1 may preferentially regulate a distinct Rad51 population associated with double-stranded DNA. Accordingly, Rrp1 can alleviate the toxicity caused by Rad51 overproduction, a function not shared by Srs2. Unexpectedly, both loss and overproduction of Srs2 promote Rad51 accumulation, suggesting that excessive helicase levels may generate ssDNA substrates that promote Rad51 nucleation. Both Srs2 and Rrp1 fail to remove strand-exchange-deficient Rad51 from DNA. Both enzymes restrict Rad51 occupancy at centromeric regions, whereas only Srs2 acts within ribosomal DNA (rDNA) repeats, revealing locus-specific regulation. Our findings support a model in which anti-recombinogenic enzymes differentially regulate Rad51 according to its DNA substrate, thereby contributing to a regulatory system that balances Rad51 functions during DNA repair across different genomic regions.

Related

  1. Structure of the human mitochondrial RNA degradosomereveals a distinct mode of helicase-nuclease coupling
    P. F. V. do Prado, S. Sharma, A. Bhatta +5
    bioRxivPreprintCC BY-NCFull textMolecular biology & gene regulationbioRxiv
  2. Neuronal lipid composition regulates distinct states of full-length tau assembly, mechanics and membrane interactions
    A. K. Mahakud, A. S. Modak, S. Singh +5
    bioRxivPreprintAll rights reservedFull textBiophysicsbioRxiv
  3. MCM10 and RECQL4 have cooperative and redundant roles in activating the CMG helicase during the replication initiation
    Atabek Bektash, Xiaoxuan Zhu, Yuki Hatoyama +2
    Genes & DevelopmentPreprintCC BY-NC 4.0Full text2 citedMolecular biology & gene regulationPMC
  4. MCM10 and SLD-2/RECQL4 jointly activate the CMG helicase during metazoan DNA replication initiation
    Remi Sonneville, Cecile Evrin, Jane Wright +3
    The EMBO JournalPeer-reviewedCC BY 4.0Full text1 citedMolecular biology & gene regulationPMC
  5. Cryo-EM structures of autoinhibited and RNA-activated ZNFX1 helicase
    Qing He, Feng Wang, Feyruz V. Rassool +2
    Nature CommunicationsPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationPMC

Cite

BibTeXRIS
BibTeX
@article{misiorna2026distinct,
  title = {{Distinct ways by which Srs2 helicase and Rrp1 translocase shape Rad51–DNA interactions in fission yeast}},
  author = {Dorota Misiorna and Dorota Dziadkowiec and Karol Kramarz},
  journal = {Nucleic Acids Research},
  year = {2026},
  month = oct,
  doi = {10.1093/nar/gkag978},
  url = {https://academic.oup.com/nar/article/doi/10.1093/nar/gkag978/8913155},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Distinct ways by which Srs2 helicase and Rrp1 translocase shape Rad51–DNA interactions in fission yeast
AU  - Dorota Misiorna
AU  - Dorota Dziadkowiec
AU  - Karol Kramarz
PY  - 2026
DA  - 2026/10/13
JO  - Nucleic Acids Research
DO  - 10.1093/nar/gkag978
UR  - https://academic.oup.com/nar/article/doi/10.1093/nar/gkag978/8913155
AB  - Precise regulation of homologous recombination is essential for genome stability. Multiple helicases and translocases prevent toxic, unscheduled association of the Rad51 recombinase with chromatin, and their levels are frequently dysregulated in cancer. It remains unclear how anti-recombinogenic enzymes act on distinct pools of Rad51. Using Schizosaccharomyces pombe, we show that the Srs2 helicase and Rrp1 translocase may target distinct Rad51 species through recombinase substrate specificity and activity control. Genetic analyses support a model in which Srs2 may preferentially regulate Rad52-dependent Rad51 nucleofilaments associated with single-stranded DNA (ssDNA), whereas Rrp1 may preferentially regulate a distinct Rad51 population associated with double-stranded DNA. Accordingly, Rrp1 can alleviate the toxicity caused by Rad51 overproduction, a function not shared by Srs2. Unexpectedly, both loss and overproduction of Srs2 promote Rad51 accumulation, suggesting that excessive helicase levels may generate ssDNA substrates that promote Rad51 nucleation. Both Srs2 and Rrp1 fail to remove strand-exchange-deficient Rad51 from DNA. Both enzymes restrict Rad51 occupancy at centromeric regions, whereas only Srs2 acts within ribosomal DNA (rDNA) repeats, revealing locus-specific regulation. Our findings support a model in which anti-recombinogenic enzymes differentially regulate Rad51 according to its DNA substrate, thereby contributing to a regulatory system that balances Rad51 functions during DNA repair across different genomic regions.
SN  - 0305-1048
SN  - 1362-4962
ER  -