Regulation of cohesin in the fission yeast S. pombe.

1) Wider research context / theoretical framework The cohesin complex mediates sister chromatid cohesion to ensure proper segregation of chromosomes. Sororin protein stabilizes cohesin on chromatin, thus enabling cohesive cohesin complexes to maintain sister chromatid cohesion from S phase until the onset of anaphase. Although sororin is a key regulator of cohesin in animal cells, sororin was thought to be absent in lower eukaryotes. 2) Hypothesis / research questions / objectives Our recent data suggest that sororin is also present in the fission yeast Schizosaccharomyces pombe. We identified previously uncharacterized S. pombe protein, namely Sor1, which shares similarities with known sororin proteins. Our recent results are consistent with the notion that Sor1 regulates cohesin in fission yeast but the function of Sor1 is not clear. The aim of this project is to test the hypothesis that this protein is a functional homolog of sororin in the fission yeast S. pombe. 3) Approach / methods Phenotypic analysis will aim to reveal whether the absence of the S. pombe Sor1 results in phenotype consistent with defects in regulation of cohesin’s function. Biochemical experiments will analyze physical interactions between the S. pombe Sor1 and cohesin as well as their localization on chromatin. 4) Level of originality / innovation Until recently, the consensus in the field was that sororin is present only in metazoans and that lower eukaryotes rely on other mechanisms that substitute for sororin’s function. Therefore, identification of yeast sororin can be seen as a breakthrough that will have an important impact on future studies of cohesin and chromosome biology. 5) Primary researchers involved As the principal investigator of this grant proposal, Dr. Juraj Gregan will be responsible for the project management and he will also perform the experimental work.