Acetylation by gcn5 regulates cdc6 phosphorylation in the s phase of the cell cycle

ABSTRACT In 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. Access through your institution Buy or subscribe

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CARM1 S217 PHOSPHORYLATION BY CDK1 IN LATE G2 PHASE FACILITATES MITOTIC ENTRY Article Open access 25 March 2025 INTERPLAY BETWEEN P300 AND HDAC1 REGULATE ACETYLATION AND STABILITY OF API5 TO

REGULATE CELL PROLIFERATION Article Open access 12 August 2021 ACETYLATION-DEPENDENT COUPLING BETWEEN G6PD ACTIVITY AND APOPTOTIC SIGNALING Article Open access 05 October 2023 REFERENCES *

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Universita' e Ricerca,” Italy and from the “Fondazione CRTrieste” of Trieste, Italy. The authors are indebted to H. Masai (Tokyo Metropolitan Institute of Medical Science) for helpful

discussion and to A. Dutta (University of Virginia), K. Helin (Biotech Research and Innovation Centre and Centre for Epigenetics), M. Benkirane (Institut de G–énétique Humaine), J. Pines

(Wellcome Trust/Cancer Research UK Gurdon Institute) and H. Masai for the gift of reagents. The authors are grateful to V. Liverani for excellent technical support and to S. Kerbavcic for

superb editorial assistance. AUTHOR INFORMATION Author notes * Roberta Paolinelli Present address: Present address: IFOM-Institute of Molecular Oncology-Foundation, Milan, Italy., * Roberta

Paolinelli and Ramiro Mendoza-Maldonado: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Molecular Biology Laboratory, Scuola Normale Superiore, AREA della Ricerca

del CNR, Pisa, Italy Roberta Paolinelli & Anna Cereseto * Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy Roberta

Paolinelli, Ramiro Mendoza-Maldonado & Mauro Giacca * Department of Biomedicine, Faculty of Medicine, University of Trieste, Italy Mauro Giacca Authors * Roberta Paolinelli View author

publications You can also search for this author inPubMed Google Scholar * Ramiro Mendoza-Maldonado View author publications You can also search for this author inPubMed Google Scholar *

Anna Cereseto View author publications You can also search for this author inPubMed Google Scholar * Mauro Giacca View author publications You can also search for this author inPubMed Google

Scholar CONTRIBUTIONS All experiments were performed by R.P. and R.M.-M.; A.C. took part in the design of the initial CDC6 acetylation experiments; M.G. supervised the work and wrote the

manuscript. CORRESPONDING AUTHOR Correspondence to Mauro Giacca. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–9 (PDF 5772 kb) RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Paolinelli, R., Mendoza-Maldonado, R., Cereseto, A. _et al._ Acetylation by GCN5 regulates CDC6 phosphorylation in the S phase

of the cell cycle. _Nat Struct Mol Biol_ 16, 412–420 (2009). https://doi.org/10.1038/nsmb.1583 Download citation * Received: 12 May 2008 * Accepted: 04 March 2009 * Published: 03 April 2009

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