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Article Dans Une Revue Molecular and Cellular Biology Année : 2005

CENP-A is required for accurate chromosome segregation and sustained kinetochore association of BubR1

Résumé

CENP-A is an evolutionarily conserved, centromere-specific variant of histone H3 that is thought to play a central role in directing kinetochore assembly and in centromere function. Here, we have analyzed the consequences of disrupting the CENP-A gene in the chicken DT40 cell line. In CENP-A-depleted cells, kinetochore protein assembly is impaired, as indicated by mislocalization of the inner kinetochore proteins CENP-I, CENP-H, and CENP-C as well as the outer components Nuf2/Hec1, Mad2, and CENP-E. However, BubR1 and the inner centromere protein INCENP are efficiently recruited to kinetochores. Following CENP-A depletion, chromosomes are deficient in proper congression on the mitotic spindle and there is a transient delay in prometaphase. CENP-A-depleted cells further proceed through anaphase and cytokinesis with unequal chromosome segregation, suggesting that some kinetochore function remains following substantial depletion of CENP-A. We furthermore demonstrate that CENP-A-depleted cells exhibit a specific defect in maintaining kinetochore localization of the checkpoint protein BubR1 under conditions of checkpoint activation. Our data thus point to a specific role for CENP-A in assembly of kinetochores competent in the maintenance of mitotic checkpoint signaling.

Dates et versions

hal-00022338 , version 1 (06-04-2006)

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Citer

Vinciane Régnier, Paola Vagnarelli, Tatsuo Fukagawa, Tatiana Zerjal, Elizabeth Burns, et al.. CENP-A is required for accurate chromosome segregation and sustained kinetochore association of BubR1. Molecular and Cellular Biology, 2005, 25 (10), pp.3967-3981. ⟨10.1128/MCB.25.10.3967-3981.2005⟩. ⟨hal-00022338⟩
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