Mislocalization of the Drosophila centromere-specific histone CIDpromotes formation of functional ectopic kinetochores
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 non-centromeric 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.
- Research Organization:
- Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
- Sponsoring Organization:
- USDOE Director, Office of Science. Office of Biological andEnvironmental Research. Life Sciences Division
- DOE Contract Number:
- AC02-05CH11231
- OSTI ID:
- 891355
- Report Number(s):
- LBNL--59454; BnR: 400412000
- Journal Information:
- Developmental Cell, Journal Name: Developmental Cell Journal Issue: 3 Vol. 10
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
60 APPLIED LIFE SCIENCES
ANEUPLOIDY
ANIMALS
CENTROMERES
CHROMOSOMES
DEFECTS
DROSOPHILA
FRAGMENTATION
FUNCTIONALS
HISTONES
INSTABILITY
MICROTUBULES
MITOSIS
MITOTIC DELAY
NEOPLASMS
PLASTICITY
PROTEINS
SEGREGATION
TISSUE CULTURES
centromere CID CENP-Akinetochore mitosis aneuploidy