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

Chakraborty, S., Strachan, J., Schirmeisen, K., Besse, L., Mercier, E., Fréon, K., Zhang, H., Zhao, N., Bayne, E.H., and Lambert, S.A.E.

By Rayane Kaade, Ohkura Lab

In this paper, Chakraborty et al investigate the dynamic cross talk between SUMOylation and ubiquitination in the nucleus of Schizosaccharomyces pombe. 

Nuclear compartmentalization and 3D genome organization have been found to be important for many aspects of genome maintenance and regulation, including chromosome segregation, transcription, and DNA repair. In many organisms including yeast, flies, and mammals, DNA lesions like double strand breaks relocate to the nuclear periphery, ensuring spatial regulation of DNA repair processes. 

SUMOylation is a post translational modification which plays various regulatory roles, including  in the relocation of damaged DNA. SUMO-targeted E3 ubiquitin ligases (STUbLs) recognize SUMOylated proteins and determine their fate, with STUbL-mediated ubiquitination directing either degradation or other non-proteolytic functions.

In this paper, the authors focus on the STUbL: Slx8, a key player in maintaining genome integrity. By live imaging in S. pombe they found that, although Slx8 was expected to form foci in response to replication stress, in unstressed cells it localizes in a single discrete focus at the nuclear periphery. This focus is dependent on SUMOylation, and further colocalization analyses showed that it is associated with two key heterochromatic genomic regions: clustered centromeres, and the silent mating-type region. Finally, they showed that Slx8 is not just passively localized to these regions, and is actively involved in promoting centromere clustering and gene silencing, important for genome stability.

This work highlights the role of STUbLs and shows their contribution to functional nuclear organization and the regulation of activity and positioning of key genomic regions within the nucleus.