The protective/regulative role of the antioxidant enzyme Irc15 on the microtubule network of S. cerevisiae

The genome of Saccharomyces cerevisiae contains 68 genes (1,1% of all yeast proteins) which encode for flavin-dependent proteins. Thirty-five flavoproteins require FAD (74%) and fifteen require FMN (26%). This utilization of FMN and FAD is similar to the distribution across all kingdoms of life. Several yeast flavoroteins could serve as convenient model system; nevertheless many yeast flavoenzymes are poorly characterized. Biochemical properties such as substrate specificity, kinetic parameters and reaction partners need to be determined to improve our understanding of human orthologs.
One flavoenzyme, which raised our interest is Irc15p (increased recombination centers 15). This protein is similar to FAD-containing lipoamide dehydrogenases, however, it lacks the internal dithiol-disulfide motif that is involved in the oxidation of lipoamide in the pyruvate dehydrogenase complex. Interestingly, Irc15p was found to be associated with microtubules and displayed an influence on the dynamics of microtubules. Loss of Irc15p function resulted in delayed mitotic progression due to the failure to establish tension between sister kinetochores. We are currently investigating the biochemical properties of recombinant Irc15p to better understand its functional role and its impact on microtubules.