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PMID: 12642611 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Differential kinetochore protein requirements for establishment versus propagation of centromere activity in Saccharomyces cerevisiae.

The Journal of cell biology ·Vol. 160 ·No. 6 ·2003-03-17 ·Pages 833-43

Mythreye K, Bloom KS

Abstract

Dicentric chromosomes undergo a breakage-fusion-bridge cycle as a consequence of having two centromeres on the same chromatid attach to opposite spindle poles in mitosis. Suppression of dicentric chromosome breakage reflects loss of kinetochore function at the kinetochore-microtubule or the kinetochore-DNA interface. Using a conditionally functional dicentric chromosome in vivo, we demonstrate that kinetochore mutants exhibit quantitative differences in their degree of chromosome breakage. Mutations in chl4/mcm17/ctf17 segregate dicentric chromosomes through successive cell divisions without breakage, indicating that only one of the two centromeres is functional. Centromere DNA introduced into the cell is unable to promote kinetochore assembly in the absence of CHL4. In contrast, established centromeres retain their segregation capacity for greater than 25 generations after depletion of Chl4p. The persistent mitotic stability of established centromeres reveals the presence of an epigenetic component in kinetochore segregation. Furthermore, this study identifies Chl4p in the initiation and specification of a heritable chromatin state.

MeSH Terms
Cell Cycle Proteins/genetics,metabolism Cells, Cultured Centromere/genetics,metabolism Chromatin/genetics,metabolism Chromosome Breakage/genetics Chromosome Segregation/physiology Kinetochores/metabolism Mitosis/physiology Mutation/genetics Plasmids/genetics,metabolism Saccharomyces cerevisiae/cytology,genetics,metabolism Saccharomyces cerevisiae Proteins
Chemicals
CHL4 protein, S cerevisiae Cell Cycle Proteins Chromatin Saccharomyces cerevisiae Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mythreye Karthikeyan
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Bloom Kerry S
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200211116
Published
2003-03-17
Pages
833-43
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173759
Subset
IM
Grants
NIGMS NIH HHS · R01 GM032238 · United States
NIGMS NIH HHS · R37 GM032238 · United States
NIGMS NIH HHS · GM32238 · United States
External Links
PubMed source DOI: 10.1083/jcb.200211116 PMC Full Text View journal details
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