PolySUMOylation restrains ubiquitination to protect fragile genomic loci during replication stress in fission yeast

Using Schizosaccharomyces pombe, we show that cells devoid of SUMO chains experience elevated, spontaneous replication stress concentrated at rDNA, accompanied by excessive recruitment of the recombination factor Rad52, independently from PCNA-K164 ubiquitination signaling. PolySUMOylation promotes completion of replication following hydroxyurea-induced stress in the absence of recombination.

Loss of SUMO chains leads to a global increase in ubiquitination and a shift in toward K63-linked ubiquitin chains. Proteomic analyses identify shared and distinct targets of Nse2 and Pli1 E3 SUMO ligases, suggesting Pli1 role at specific genomic loci such as rDNA. Chromatin mapping demonstrated enrichment of both ligases at rDNA, centromeres, telomeres, and other fragile genomic regions.