Nucleic Acids Research, Vol 27, Issue 15 3001-3008, Copyright © 1999 by Oxford University Press
II Ouspenski, SJ Elledge and BR Brinkley
Phenotypes produced by gene overexpression may provide important clues to
gene function. Here, we have performed a search for genes that affect
chromo-some stability when overexpressed in the budding yeast Saccharomyces
cerevisiae. We have obtained clones encompassing 30 different genes.
Twenty-four of these genes have been previously characterized. Most of them
are involved in chromatin dynamics, cell cycle control, DNA replication or
mitotic chromosome 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 specifically interferes with mitotic chromosome
segregation, and CST6 affects some aspect of DNA metabolism. The other CST
genes had complex pleiotropic phenotypes. We have created deletions of five
genes obtained in this screen, CST9, CST13, NAT1, SBA1 and FUN30. None of
these genes is essential for viability, and deletions of NAT1 and SBA1
cause chromosome instability, a phenotype not previously associated with
these genes. This work shows that analysis of dosage effects is
complementary to mutational analysis of chromosome transmission fidelity,
as it allows the identification of chromosome stability genes that have not
been detected in mutational screens.
ARTICLES
New yeast genes important for chromosome integrity and segregation identified by dosage effects on genome stability
Department of Cell Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. iliao@bcm.tmc.edu
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