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Mol Biol Cell. 2009 Oct;20(19):4194-204. doi: 10.1091/mbc.E09-06-0489. Epub 2009 Aug 5.

Hierarchical inactivation of a synthetic human kinetochore by a chromatin modifier.

Author information

1
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.

Abstract

We previously used a human artificial chromosome (HAC) with a synthetic kinetochore that could be targeted with chromatin modifiers fused to tetracycline repressor to show that targeting of the transcriptional repressor tTS within kinetochore chromatin disrupts kinetochore structure and function. Here we show that the transcriptional corepressor KAP1, a downstream effector of the tTS, can also inactivate the kinetochore. The disruption of kinetochore structure by KAP1 subdomains does not simply result from loss of centromeric CENP-A nucleosomes. Instead it reflects a hierarchical disruption of the outer kinetochore, with CENP-C levels falling before CENP-A levels and, in certain instances, CENP-H being lost more readily than CENP-C. These results suggest that this novel approach to kinetochore dissection may reveal new patterns of protein interactions within the kinetochore.

PMID:
19656847
PMCID:
PMC2754933
DOI:
10.1091/mbc.e09-06-0489
[Indexed for MEDLINE]
Free PMC Article

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