The fission yeast SUMO-targeted Ubiquitin Ligase Slx8 functionally associates with clustered centromeres and the silent mating type region at the nuclear periphery

The SUMO-targeted Ubiquitin ligase (STUbL) family is involved in multiple cellular processes via a wide range of mechanisms to maintain genome stability. One of the evolutionarily conserved functions of STUbL is to promote changes in the nuclear positioning of DNA lesions, targeting them to the nuclear periphery. In Schizossacharomyces pombe, the STUbL Slx8 is a regulator of SUMOylated proteins and promotes replication stress tolerance by counteracting the toxicity of SUMO conjugates. In order to study the dynamic dialectic between Ubiquitinylation and SUMOylation in the nuclear space of the S. pombe genome, we analyzed Slx8 localization. Unexpectedly, we did not detect replication stress-induced Slx8 foci. However, we discovered that Slx8 forms a single nuclear focus, enriched at the nuclear periphery, which marks both clustered centromeres at the spindle pole body and the silent mating type region. The formation of this single Slx8 focus requires the E3 SUMO ligase Pli1, poly-SUMOylation and the histone methyl transferase Clr4 that is responsible for the heterochromatin histone mark H3-K9 methylation. Finally, we established that Slx8 promotes centromere clustering and gene silencing at heterochromatin domains. Altogether, our data highlight evolutionarily conserved and functional relationships between STUbL and heterochromatin domains to promote gene silencing and nuclear organization. HighlightsO_LIThe S. pombe STUbL Slx8 forms a single nuclear focus enriched at the nuclear periphery in a SUMO-chain-dependent manner. C_LIO_LISlx8 foci mark clustered centromeres and the silenced mating type region but not telomeres. C_LIO_LIH3-K9 methylation by Crl4 promotes the single nuclear Slx8 focus C_LIO_LISlx8 promotes centromere clustering and gene silencing. C_LI