Cdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle Progression

• Autor(a) principal: Silva, Mariana C.C.
• Data de Publicação: 2012
• Outros Autores: Bodor, Dani L., Stellfox, Madison E., Martins, Nuno M.C., Hochegger, Helfrid, Foltz, Daniel R., Jansen, Lars E.T.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.7/616
• topic: 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

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.