New yeast genes important for chromosome integrity and segregation identified by dosage effects on genome stability

Phenotypes produced by gene overexpression may provide important clues to g ene function. Here, we have performed a search for genes that affect chromo some stability when overexpressed in the budding yeast Saccharomyces cerevi siae, We have obtained clones encompassing 30 different genes, Twenty-four of these genes have been previously characterized. Most of them are involve d in chromatin dynamics, cell cycle control, DNA replication or mitotic chr omosome segregation. Six novel genes obtained in this screen were named CST (chromosome stability), Based on the pattern of genomic instability, inter action with checkpoint mutations and sensitivity to chromosome replication or segregation inhibitors, we conclude that overexpression of CST4 specific ally interferes with mitotic chromosome segregation, and CST6 affects some aspect of DNA metabolism, The other CST genes had complex pleiotropic pheno types. We have created deletions of five genes obtained in this screen, CST 9, CST13, NAT1, SBA1 and FUN30, None of these genes is essential for viabil ity, and deletions of NAT1 and SBA1 cause chromosome instability, a phenoty pe not previously associated with these genes, This work shows that analysi s of dosage effects is complementary to mutational analysis of chromosome t ransmission fidelity, as it allows the identification of chromosome stabili ty genes that have not been detected in mutational screens.