Cdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle Progression

Mariana C C Silva, Dani L. Bodor, Madison E. Stellfox, Nuno M C Martins, Helfrid Hochegger, Daniel R. Foltz, Lars E T Jansen

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)52-63
Number of pages12
JournalDevelopmental Cell
Volume22
Issue number1
DOIs
StatePublished - Jan 17 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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