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EnglishIn eukaryotic cells, the cell-division cycle (CDC)-6 protein is essential to promote the assembly of pre-replicative complexes in the early G1 phase of the cell cycle, a process requiring tight regulation to ensure that proper origin licensing occurs once per cell cycle. Here we show that, in late G1 and early S phase, CDC6 is found in a complex also containing Cyclin A, cyclin-dependent kinase (CDK)-2 and the acetyltransferase general control nonderepressible 5 (GCN5). GCN5 specifically acetylates CDC6 at three lysine residues flanking its cyclin-docking motif, and this modification is crucial for the subsequent phosphorylation of the protein by Cyclin A-CDKs at a specific residue close to the acetylation site. GCN5-mediated acetylation and site-specific phosphorylation of CDC6 are both necessary for the relocalization of the protein to the cell cytoplasm in the S phase, as well as to regulate its stability. This two-step, intramolecular regulatory program by sequential modification of CDC6 seems to be essential for proper S-phase progression.
| Titolo: | Acetylation by GCN5 regulates CDC6 phosphorylation in the S phase of the cell cycle. | |
| Autori: | R., Paolinelli; R., Mendoza Maldonado; Cereseto, Anna; M., Giacca | |
| Autori Unitn: | ||
| Titolo del periodico: | NATURE STRUCTURAL & MOLECULAR BIOLOGY | |
| Anno di pubblicazione: | 2009 | |
| Codice identificativo Scopus: | 2-s2.0-64049105933 | |
| Codice identificativo Pubmed: | 19343071 | |
| Codice identificativo WOS: | WOS:000264892300014 | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/nsmb.1583 | |
| Handle: | http://hdl.handle.net/11572/34278 | |
| Appare nelle tipologie: | 03.1 Articolo su rivista (Journal article) |
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