The role of Schizosaccharomyces pombe SUMO ligases in genome stability

Abstract

SUMOylation is a post-translational modification that affects a large number of proteins, many of which are nuclear. While the role of SUMOylation is beginning to be elucidated, it is clear that understanding the mechanisms that regulate the process is likely to be important. Control of the levels of SUMOylation is brought about through a balance of conjugating and deconjugating activities, i.e. of SUMO (small ubiquitin-related modifier) conjugators and ligases versus SUMO proteases. Although conjugation of SUMO to proteins can occur in the absence of a SUMO ligase, it is apparent that SUMO ligases facilitate the SUMOylation of specific subsets of proteins. Two SUMO ligases in Schizosaccharomyces pombe, Pli1 and Nse2, have been identified, both of which have roles in genome stability. We report here on a comparison between the properties of the two proteins and discuss potential roles for the proteins.

DNA Repair and Global Sumoylation Are Regulated by Distinct Ubc9 Noncovalent Complexes

“…It is also unclear whether the observed binding of Rad60 SLD2 to Ubc9 (39) antagonizes SUMO chain formation by disrupting the Ubc9:SUMO complex (42). In addition, whether the major SUMO E3 ligase Pli1 and its homologs Siz1/Siz2 of budding yeast and PIAS (protein inhibitor of activated STAT)-type ligases of higher eukaryotes (51) play a key role in forming SUMO chains remains unanswered.…”

“…Cells lacking Pli1 exhibit greatly reduced levels of global SUMO conjugates, heterochromatin silencing defects, and altered telomere length but are insensitive to genotoxins (38,51,56). Conversely, Nse2 SUMO E3 ligase-deficient cells lack the major Pli1 mutant phenotypes and are hypersensitive to genotoxic stress (51).…”

“…The ubiquitin modification system has a similar enzymatic cascade, but in stark contrast to the SUMO pathway, it has multiple E2s and numerous E3 ligases that provide a clear basis for selectivity (20). For example, in the fission yeast Schizosaccharomyces pombe the SUMO pathway includes a single E2 called Ubc9 (Hus5) and two known SUMO E3 ligases, Pli1 and Nse2 (51). Although these two E3 ligases are responsible for sumoylating largely distinct targets, how substrate specificity is generated is poorly characterized.…”

“…Cells lacking Pli1 exhibit greatly reduced levels of global SUMO conjugates, heterochromatin silencing defects, and altered telomere length but are insensitive to genotoxins (38,51,56). Conversely, Nse2 SUMO E3 ligase-deficient cells lack the major Pli1 mutant phenotypes and are hypersensitive to genotoxic stress (51). Nse2 (Mms21 of the budding yeast Saccharomyces cerevisiae) is part of the essential Smc5/6 complex that plays critical roles in DNA repair and suppressing aberrant recombination (3,6,11,12,14,36).…”

Eukaryotic Replication Barriers: How, Why and Where Forks Stall

“…Rtf2 is the defining member of a family of proteins that are conserved from S. pombe to humans, which are characterized by the presence of a novel type of C2HC2 ring finger motif that potentially only binds one Zn 2+ atom. A similar Ring finger motif, named the SP motif, with only one Zn 2+ -atom binding site, is found in many E3 SUMO ligases including S. cerevisiae Siz1, Siz2; S. pombe Pli1, Nse2; human PIAS1, PIASxβ, PIAS3, PIASy, Mms21 (Watts, et al 2007;Yunus & Lima, 2009) and an epistasis analysis suggests that Rtf2 and SUMO (pmt3) might act together in the same pathway (Inagawa, et al 2009). However, Rtf2 also seems to have a role that is independent of SUMO, as slow moving replication forks are present at the RTS1 element in the Rtf2 single mutant that are absent in the SUMO single mutant.…”