期刊
DEVELOPMENTAL CELL
卷 22, 期 1, 页码 52-63出版社
CELL PRESS
DOI: 10.1016/j.devcel.2011.10.014
关键词
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资金
- Fundacao para a Ciencia e a Tecnologia (FCT) [SFRH/BD/33219/2007, BIA-BCM/100557/2008]
- Fundacao Calouste Gulbenkian
- European Commission
- EMBO
- Medical Research Council [G0801130B] Funding Source: researchfish
- Fundação para a Ciência e a Tecnologia [SFRH/BD/33219/2007] Funding Source: FCT
Centromeres form the site of chromosome attachment to microtubules during mitosis. Identity of these loci is maintained epigenetically by nucleosomes containing the histone H3 variant CENP-A. Propagation of CENP-A chromatin is uncoupled from DNA replication initiating only during mitotic exit. We now demonstrate that inhibition of Cdk1 and Cdk2 activities is sufficient to trigger CENP-A assembly throughout the cell cycle in a manner dependent on the canonical CENP-A assembly machinery. We further show that the key CENP-A assembly factor Misl SSP-II-Ism-2 is phosphorylated in a cell cycledependent manner that controls its centromere localization during mitotic exit. These results strongly support a model in which the CENP-A assembly machinery is poised for activation throughout the cell cycle but kept in an inactive noncentromeric state by Cdk activity during S, G2, and M phases. Alleviation of this inhibition in G1 phase ensures tight coupling between DNA replication, cell division, and subsequent centromere maturation.
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