Cdk activity couples epigenetic centromere inheritance to cell cycle progression

Dev Cell. 2012 Jan 17;22(1):52-63. doi: 10.1016/j.devcel.2011.10.014. Epub 2011 Dec 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / metabolism*
  • Blotting, Western
  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle
  • Cell Division
  • Centromere / physiology*
  • Centromere Protein A
  • Chromatin / genetics
  • Chromosomal Proteins, Non-Histone / antagonists & inhibitors
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cyclin-Dependent Kinase 2 / metabolism*
  • Epigenomics*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • G1 Phase / physiology*
  • HeLa Cells
  • Humans
  • Mitosis / physiology
  • Phosphorylation


  • Autoantigens
  • CENPA protein, human
  • Centromere Protein A
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • MIS18BP1 protein, human
  • CDC2 Protein Kinase
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2