Suppressor analysis of histone mutants defective in chromosome segregation.
Hasna Kanta, Marsha Rhoads, Inés Pinto
Biological Sciences, University of Arkansas, SCEN 601, Fayetteville, AR, 72701, USA
Previous characterization of histone H2A mutants that display extreme chromosome instabilities, ranging from chromosome loss to duplication of their entire genome (increase in ploidy), led us to conclude that histone H2A is required for normal centromere-kinetochore function. To identify the factors that interact with histone H2A in establishing a functional centromere, a mutant screen was carried out to identify mutations that suppress the increase-in-ploidy phenotype of the H2A mutants. Two uncharacterized genes were identified and designated PLO1 and PLO2 (ploidy suppressor). PLO1 and PLO2 encode proteins with significant homology to each other. Deletion of PLO1 causes pleiotropic phenotypes: cold sensitivity, slow growth, and a G2/M delay after DNA replication. We have recently identified another suppressor, hda1, which encodes a histone deacetylase. Hda1 forms a complex with Plo1/Hda3 and Plo2/Hda2. These suppressors provide the first connection between histone deacetylase activity and centromere function in S. cerevisiae. Each member of the complex shows allele specificity with respect to the suppressor phenotype. In addition, the pleiotropic phenotypes caused by a plo1-delta are not seen in plo2-delta or hda1-delta strains, suggesting additional roles for Plo1/Hda3. Our current studies are directed to addressing the role of this complex as a suppressor of the histone defect and the involvement of deacetylase function in chromosome segregation and stability.
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