Quality Control of a Transcriptional Regulator by SUMO-targeted Degradation

MOT1 encodes an essential ATPase that functions as a general transcriptional regulator in vivo by modulating TATA-Binding Protein (TBP) DNA-binding activity. To better understand the role(s) of MOT1 in vivo, we selected for genomic suppressors of a mot1 temperature-sensitive (Ts-) mutation. This selection identified mutations in SPT15 (TBP) and BUR6, both of which are clearly linked with MOT1 at the functional level. The vast majority of the suppressor mutations, however, unexpectedly occurred in six genes that encode known components of the SUMO pathway and in two other genes with unknown functions, SLX5 and SLX8. The results presented in Chapter I, including extensive synthetic lethality observed between slx5Delta and slx8Delta and SUMO pathway mutations, as well as increased SUMOylation levels in slx5Delta and slx8Delta strains, suggest that SLX5 and SLX8 are new components or regulators of the SUMO pathway.