Journal
JOURNAL OF CELL BIOLOGY
Volume 190, Issue 2, Pages 177-185Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201001035
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Funding
- National Institutes of Health [GM82989]
- Burroughs Wellcome Fund
- Rita Allen Foundation
- University of Pennsylvania (National Institutes of Health) [GM08275]
- American Heart Association
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T he nearly ubiquitous presence of repetitive centromere DNA sequences across eukaryotic species is in paradoxical contrast to their apparent functional dispensability. Centromeric chromatin is spatially delineated into the kinetochore-forming array of centromere protein A (CENP-A)-containing nucleosomes and the inner centromeric heterochromatin that lacks CENP-A but recruits the aurora B kinase that is necessary for correcting erroneous attachments to the mitotic spindle. We found that the self-perpetuating network of CENPs at the foundation of the kinetochore is intact at a human neocentromere lacking repetitive alpha-satellite DNA. However, aurora B is inappropriately silenced as a consequence of the altered geometry of the neocentromere, thereby compromising the error correction mechanism. This suggests a model wherein the neocentromere represents a primordial inheritance locus that requires subsequent generation of a robust inner centromere compartment to enhance fidelity of chromosome transmission.
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