title: Centromeric barrier disruption leads to mitotic defects in Schizosaccharomyces pombe.
abstract: Centromeres are cis-acting chromosomal domains that direct kinetochore formation, enabling faithful chromosome segregation and preserving genome stability. The centromeres of most eukaryotic organisms are structurally complex, composed of nonoverlapping, structurally and functionally distinct chromatin subdomains, including the specialized core chromatin that underlies the kinetochore and pericentromeric heterochromatin. The genomic and epigenetic features that specify and preserve the adjacent chromatin subdomains critical to centromere identity are currently unknown. Here we demonstrate that chromatin barriers regulate this process in Schizosaccharomyces pombe. Reduced fitness and mitotic chromosome segregation defects occur in strains that carry exogenous DNA inserted at centromere 1 chromatin barriers. Abnormal phenotypes are accompanied by changes in the structural integrity of both the centromeric core chromatin domain, containing the conserved CENP-A(Cnp1) protein, and the flanking pericentric heterochromatin domain. Barrier mutant cells can revert to wild-type growth and centromere structure at a high frequency after the spontaneous excision of integrated exogenous DNA. Our results reveal a previously undemonstrated role for chromatin barriers in chromosome segregation and in the prevention of genome instability.
authors: Institute for Genome Sciences and Policy, Duke University, DUMC 3382, Durham, North Carolina 27708, and.
authors: Terilyn L
authors: TL
authors: Gaither
authors: Stephanie L
authors: SL
authors: Merrett
authors: Matthew J
authors: MJ
authors: Pun
authors: Kristin C
authors: KC
authors: Scott
mesh_terms: D002503:Centromere / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D042822:Genomic Instability; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C410349:Cnp1 protein, S pombe; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins
keywords: CENP-A; barrier; centromere; chromatin; genome instability