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  Mislocalization of the Drosophila Centromere-Specific Histone CID Promotes Formation of Functional Ectopic Kinetochores

Heun, P., Erhardt, S., Blower, M. D., Weiss, S., Skora, A. D., & Karpen, G. H. (2006). Mislocalization of the Drosophila Centromere-Specific Histone CID Promotes Formation of Functional Ectopic Kinetochores. Developmental Cell, 10, 303-315.

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 Urheber:
Heun, Patrick1, Autor           
Erhardt, Sylvia, Autor
Blower, Michael D., Autor
Weiss, Samara, Autor
Skora, Andrew D., Autor
Karpen, Gary H., Autor
Affiliations:
1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

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 Zusammenfassung: The centromere-specific histone variant CENP-A (CID in Drosophila) is a structural and functional foundation for kinetochore formation and chromosome segregation. Here, we show that overexpressed CID is mislocalized into normally noncentromeric regions in Drosophila tissue culture cells and animals. Analysis of mitoses in living and fixed cells reveals that mitotic delays, anaphase bridges, chromosome fragmentation, and cell and organismal lethality are all direct consequences of CID mislocalization. In addition, proteins that are normally restricted to endogenous kinetochores assemble at a subset of ectopic CID incorporation regions. The presence of microtubule motors and binding proteins, spindle attachments, and aberrant chromosome morphologies demonstrate that these ectopic kinetochores are functional. We conclude that CID mislocalization promotes formation of ectopic centromeres and multicentric chromosomes, which causes chromosome missegregation, aneuploidy, and growth defects. Thus, CENP-A mislocalization is one possible mechanism for genome instability during cancer progression, as well as centromere plasticity during evolution.

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Sprache(n): eng - English
 Datum: 2006-03
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 293383
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Titel: Developmental Cell
  Alternativer Titel : Dev. Cell
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 10 Artikelnummer: - Start- / Endseite: 303 - 315 Identifikator: -