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- Title
P159 - HIR2P ACTS TO CONSTRAIN ECTOPIC LOCALIZATION OF CENTOMERIC H3 VARIANT CSE4P IN SACCROMYCES CEREVISIAE.
- Authors
CİFTCİ-YİLMAZ, Sultan; Wei CHUN AU; CHANG, Joy; DAWSON, Anthony; BOECKMANN, Lars; COSTANZO, Michael; BAKER, Richard; BOONE, Charlie; BASRAİ, Munira
- Abstract
Kinetochore (CEN DNA and associated proteins) plays a pivotal role in ensuring chromosome transmission fidelity (ctf). Centromeric localization of the evolutionarily conserved histone H3 variant Cse4p is required for centromere identity and kinetochore assembly in S. cerevisiae. There is increasing evidence that failure to exclude Cse4p from non-centromeric loci leads to chromosome loss during mitosis and the severity of the phenotype is dependent on the chromosomal location and level of mis-localization of Cse4p. To probe the molecular mechanisms underlying the exclusion of Cse4p from non-centromeric loci, we created and tested mutant alleles of cse4 in genetic and biochemical assays. Overexpression of a CSE4 mutant lacking the entire N-terminal tail (GALΔ129cse4) leads to its chromatin enrichment, increased protein stability, mis-localization and a ctf phenotype. We performed a genome-wide analysis on GALCSE4 or GALΔ129cse4 using the Synthetic Genetic Array (SGA) approach to identify genes that exclude Cse4p from non-centromeric loci by interaction with its N terminal tail. Analysis of genetic interactions specific for GALCSE4 led to the identification of genes required for ubiquitin-mediated proteolytic pathway and histone chaperone function. Our results showed that overexpression of CSE4 in histone chaperone mutant strains leads to chromatin enrichment, increased protein stability, and mis-localization of Cse4p. These investigations supported the role of histone chaperones in excluding Cse4p from non-centromeric loci. Based on our results we propose a model in which recognition of the N-terminal tail of Cse4p by a surveillance mechanism results in its exclusion from non-centromeric loci and this is required for faithful chromosome segregation.
- Subjects
CHROMOSOMES; CENTROMERE; HISTONES
- Publication
Turkish Journal of Biochemistry / Turk Biyokimya Dergisi, 2012, Vol 37, Issue S1, p300
- ISSN
0250-4685
- Publication type
Abstract