title: Structural integrity of centromeric chromatin and faithful chromosome segregation requires Pat1.
abstract: The kinetochore (centromeric DNA and associated protein complex) is essential for faithful chromosome segregation and maintenance of genome stability. Here we report that an evolutionarily conserved protein Pat1 is a structural component of Saccharomyces cerevisiae kinetochore and associates with centromeres in a NDC10-dependent manner. Consistent with a role for Pat1 in kinetochore structure and function, a deletion of PAT1 results in delay in sister chromatid separation, errors in chromosome segregation, and defects in structural integrity of centromeric chromatin. Pat1 is involved in topological regulation of minichromosomes as altered patterns of DNA supercoiling were observed in pat1Δ cells. Studies with pat1 alleles uncovered an evolutionarily conserved region within the central domain of Pat1 that is required for its association with centromeres, sister chromatid separation, and faithful chromosome segregation. Taken together, our data have uncovered a novel role for Pat1 in maintaining the structural integrity of centromeric chromatin to facilitate faithful chromosome segregation and proper kinetochore function.
authors.affiliation: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Mishra
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Ottmann
authors.forename: Munira A
authors.initials: MA
authors.lastname: Basrai
mesh_terms: D002503:Centromere / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D012854:Sister Chromatid Exchange / Q000235:genetics
chemical_list: C081071:CBF2 protein, S cerevisiae; D002843:Chromatin; D004268:DNA-Binding Proteins; C103266:PAT1 protein, S cerevisiae; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA
keywords: Centromere; DNA topology; budding yeast; chromosome segregation; kinetochore
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