Structural Integrity of Centromeric Chromatin and Faithful Chromosome Segregation Requires Pat1

Overview

Journal Genetics

Publisher Oxford University Press

Specialty Genetics

Date 2013 Jul 30

PMID 23893485

Citations 16

Authors

Prashant K Mishra

Alicia R Ottmann

Munira A Basrai

Affiliations

Soon will be listed here.

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.

Citing Articles

Misregulation of cell cycle-dependent methylation of budding yeast CENP-A contributes to chromosomal instability.

Mishra P, Au W, Castineira P, Ali N, Stanton J, Boeckmann L Mol Biol Cell. 2023; 34(10):ar99.

PMID: 37436802 PMC: 10551700. DOI: 10.1091/mbc.E23-03-0108.

Rio1 downregulates centromeric RNA levels to promote the timely assembly of structurally fit kinetochores.

Smurova K, Damizia M, Irene C, Stancari S, Berto G, Perticari G Nat Commun. 2023; 14(1):3172.

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DNA topoisomerase 2-associated proteins PATL1 and PATL2 regulate the biogenesis of hERG K channels.

Yao L, Ruan M, Ye S, Cai S Proc Natl Acad Sci U S A. 2023; 120(2):e2206146120.

PMID: 36608291 PMC: 9926248. DOI: 10.1073/pnas.2206146120.

The protective role of MC1R in chromosome stability and centromeric integrity in melanocytes.

Li X, Mao W, Chen J, Goding C, Cui R, Xu Z Cell Death Discov. 2021; 7(1):111.

PMID: 34001865 PMC: 8128912. DOI: 10.1038/s41420-021-00499-9.

R-loops at centromeric chromatin contribute to defects in kinetochore integrity and chromosomal instability in budding yeast.

Mishra P, Chakraborty A, Yeh E, Feng W, Bloom K, Basrai M Mol Biol Cell. 2020; 32(1):74-89.

PMID: 33147102 PMC: 8098821. DOI: 10.1091/mbc.E20-06-0379.

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