Regulation of Budding Yeast Kinetochore Proteins by SUMO Modification

In the first study, genes that are linked to chromosome stability were identified by performing genome-wide synthetic lethal screens using a series of novel temperature sensitive mutations in essential genes encoding a central (SPC24) and outer (SPC34) kinetochore protein. By performing these screens using different mutant alleles of each gene, we aimed to identify genetic interactions that revealed diverse pathways affecting chromosome stability. This study, which is the first example of genome-wide synthetic lethal screening with multiple alleles of a single gene, demonstrated that functionally distinct mutants uncover different cellular processes required for chromosome maintenance. Two of our screens identified APQ12, a gene that encodes a nuclear envelope protein required for proper nucleocytoplasmic transport of mRNA, which was subsequently characterized with respect to chromosome stability. We found that apq12 mutants are delayed in anaphase, re-replicate their DNA and re-bud prior to completion of cytokinesis, suggesting a defect in controlling mitotic progression. Overall, this analysis revealed a novel relationship between nucleocytoplasmic transport and chromosome stability.