PolySUMOylation of PCNA and Rad52 restricts centromeric recombination in fission yeast
SUMOylation, a conserved post-translational modification in eukaryotes, regulates protein function, localization, and stability. However, the role of SUMO chains in genome maintenance is still emerging. Using Schizosaccharomyces pombe, we show that loss of SUMO chains results in spontaneous replication stress, DNA damage, and elevated centromeric recombination. To investigate SUMO-dependent interactome at the sites of Rad52 repair, we used a split-SUMO-ID proteomics approach. It allows the analysis of local SUMOylation content at the Rad52 repair sites, and enabled the identification of the essential replication factor PCNA. We found that SUMO chain-modified PCNA antagonizes Rad8-mediated PCNA polyubiquitination, modulating the choice of post-replication repair pathways at stalled forks within centromeres. In the absence of polySUMOylation, excessive PCNA polyubiquitination drives elevated recombination at centromeres. Artificial tethering of a SUMO chain to Rad52 suppresses this defect. Our findings uncover an essential role for SUMO chains in centromere maintenance by modulating DNA repair pathway choice under endogenous replication stress.
Authors
- Julia Kończak (ORCID: https://orcid.org/0000-0001-8621-2319)
- Paulina Tomaszewska (ORCID: https://orcid.org/0000-0002-9596-7219)
- Karol Kramarz (ORCID: https://orcid.org/0000-0001-9924-3106)
- Michał Tracz (ORCID: https://orcid.org/0000-0001-7510-5024)
- Katarzyna Markowska (ORCID: https://orcid.org/0000-0001-5662-4734)
- Ireneusz Litwin (ORCID: https://orcid.org/0000-0002-2764-0708)
- Dorota Misiorna (ORCID: https://orcid.org/0000-0001-6784-672X)
- Aleksandra Bogdańska (ORCID: https://orcid.org/0009-0003-3083-0603)
- Mika Haenen
Institutions
- University of Kashmir (IN)
- University of Leicester (GB)
- University of Wrocław (PL)
- IONICS Mass Spectrometry (Canada) (CA)
- Genomics (United Kingdom) (GB)
- Cooperative Research Centre for Tissue Growth and Repair (AU)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-02
- DOI
- https://doi.org/10.1038/s41467-025-65862-1
- Primary Topic
- Ubiquitin and proteasome pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Uniwersytet Wrocławski