Cdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle Progression

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

http://hdl.handle.net/10400.7/616

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Abstract(s)

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.

Keywords

Autoantigens Blotting, Western CDC2 Protein Kinase Cell Cycle Cell Division Centromere Chromatin Chromosomal Proteins, Non-Histone Cyclin-Dependent Kinase 2 Flow Cytometry Fluorescent Antibody Technique G1 Phase HeLa Cells Humans Mitosis Phosphorylation Epigenomics

URI

http://hdl.handle.net/10400.7/616

Citation

Mariana C.C. Silva, Dani L. Bodor, Madison E. Stellfox, Nuno M.C. Martins, Helfrid Hochegger, Daniel R. Foltz, Lars E.T. Jansen, Cdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle Progression, Developmental Cell, Volume 22, Issue 1, 17 January 2012, Pages 52-63, ISSN 1534-5807, http://dx.doi.org/10.1016/j.devcel.2011.10.014.