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Structure, dynamics, and evolution of centromeric nucleosomes.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2007 Oct 09; Vol. 104 (41), pp. 15974-81. Date of Electronic Publication: 2007 Sep 24. - Publication Year :
- 2007
-
Abstract
- Centromeres are defining features of eukaryotic chromosomes, providing sites of attachment for segregation during mitosis and meiosis. The fundamental unit of centromere structure is the centromeric nucleosome, which differs from the conventional nucleosome by the presence of a centromere-specific histone variant (CenH3) in place of canonical H3. We have shown that the CenH3 nucleosome core found in interphase Drosophila cells is a heterotypic tetramer, a "hemisome" consisting of one molecule each of CenH3, H4, H2A, and H2B, rather than the octamer of canonical histones that is found in bulk nucleosomes. The surprising discovery of hemisomes at centromeres calls for a reevaluation of evidence that has long been interpreted in terms of a more conventional nucleosome. We describe how the hemisome structure of centromeric nucleosomes can account for enigmatic properties of centromeres, including kinetochore accessibility, epigenetic inheritance, rapid turnover of misincorporated CenH3, and transcriptional quiescence of pericentric heterochromatin. Structural differences mediated by loop 1 are proposed to account for the formation of stable tetramers containing CenH3 rather than stable octamers containing H3. Asymmetric CenH3 hemisomes might interrupt the global condensation of octameric H3 arrays and present an asymmetric surface for kinetochore formation. We suggest that this simple mechanism for differentiation between centromeric and packaging nucleosomes evolved from an archaea-like ancestor at the dawn of eukaryotic evolution.
- Subjects :
- Animals
Archaea chemistry
Archaea genetics
Archaea ultrastructure
Biological Evolution
Centromere genetics
Centromere metabolism
Drosophila genetics
Drosophila metabolism
Drosophila ultrastructure
HeLa Cells
Histones chemistry
Histones genetics
Histones metabolism
Humans
Kinetochores chemistry
Kinetochores ultrastructure
Microscopy, Atomic Force
Models, Molecular
Molecular Chaperones metabolism
Multiprotein Complexes
Nucleosomes genetics
Nucleosomes metabolism
Protein Structure, Quaternary
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae ultrastructure
Centromere chemistry
Centromere ultrastructure
Nucleosomes chemistry
Nucleosomes ultrastructure
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 104
- Issue :
- 41
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 17893333
- Full Text :
- https://doi.org/10.1073/pnas.0707648104