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Pat1 regulates kinetochore function by modulating the topological structure of centromeric chromatin

Friday, November 08, 2013 — Poster Session III

10:00 a.m. – 12:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • P.K. Mishra
  • A.R. Ottmann
  • M.A. Basrai


High fidelity chromosome segregation is essential for normal cell proliferation because errors in this process cause aneuploidy, a direct cause of birth defects and a hallmark of cancer. The kinetochore (centromeric DNA and associated proteins) is essential for faithful chromosome segregation. Here we report that Pat1, an evolutionarily conserved protein, is a structural component of budding yeast kinetochore. Pat1 interacts with kinetochore protein Scm3 in vivo, and associates with centromeres in the presence of a functional kinetochore. The deletion of Pat1 affects the structural integrity of centromeric chromatin and causes defects in sister chromatid separation, reduction in centromeric-Scm3, and errors in chromosome segregation. Pat1 is involved in topological regulation of minichromosomes as altered patterns of DNA supercoiling were observed in pat1∆ cells. Using mutant alleles, we have identified a functional Chromosome Transmission Fidelity domain of Pat1 and determined that the role of Pat1 in chromosome segregation is independent of its function in P-body assembly, and translation repression. Genetic alterations of Pat1 has been observed in several cancers, however the biological relevance of these observation remains unclear. Our results have uncovered a novel role for Pat1 in maintaining the structural integrity of centromeric chromatin to facilitate faithful chromosome segregation.

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