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Cdk activity couples epigenetic centromere inheritance to cell cycle progression

journal contribution
posted on 2023-06-08, 12:36 authored by Marina C C Silva, Dani L Bodor, Stellfox E Madison, Nuno M C Martins, Helfrid HocheggerHelfrid Hochegger, Daniel R Foltz, Lars E T Jansen
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 Mis18BP1(HsKNL2) is phosphorylated in a cell cycle-dependent 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

History

Publication status

  • Published

Journal

Developmental Cell

ISSN

1534-5807

Publisher

Elsevier

Issue

1

Volume

22

Page range

52-63

Department affiliated with

  • Evolution, Behaviour and Environment Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-11-01

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