title: The histone deacetylases sir2 and rpd3 act on ribosomal DNA to control the replication program in budding yeast.
abstract: In S. cerevisiae, replication timing is controlled by epigenetic mechanisms restricting the accessibility of origins to limiting initiation factors. About 30% of these origins are located within repetitive DNA sequences such as the ribosomal DNA (rDNA) array, but their regulation is poorly understood. Here, we have investigated how histone deacetylases (HDACs) control the replication program in budding yeast. This analysis revealed that two HDACs, Rpd3 and Sir2, control replication timing in an opposite manner. Whereas Rpd3 delays initiation at late origins, Sir2 is required for the timely activation of early origins. Moreover, Sir2 represses initiation at rDNA origins, whereas Rpd3 counteracts this effect. Remarkably, deletion of SIR2 restored normal replication in rpd3Δ cells by reactivating rDNA origins. Together, these data indicate that HDACs control the replication timing program in budding yeast by modulating the ability of repeated origins to compete with single-copy origins for limiting initiation factors.
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier, France; Equipe Labellisée Ligue Contre le Cancer, 14 rue Corvisart, 75013 Paris, France; Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier, France; Equipe Labellisée Ligue Contre le Cancer, 14 rue Corvisart, 75013 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Bacal
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier, France; Equipe Labellisée Ligue Contre le Cancer, 14 rue Corvisart, 75013 Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Desmarais
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier, France; Equipe Labellisée Ligue Contre le Cancer, 14 rue Corvisart, 75013 Paris, France.
authors.forename: Ismaël
authors.initials: I
authors.lastname: Padioleau
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå Sweden.
authors.forename: Olga
authors.initials: O
authors.lastname: Tsaponina
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå Sweden.
authors.forename: Andrei
authors.initials: A
authors.lastname: Chabes
authors.affiliation: Inserm U847, Centre Hospitalier Universitaire de Montpellier, Institut de Recherche en Biothérapie, Hôpital Saint Eloi, Université Montpellier 1, Montpellier F-34000, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Pantesco
authors.affiliation: MGX-Montpellier GenomiX, c/o Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, F-34094 Montpellier Cedex 5, France.
authors.forename: Emeric
authors.initials: E
authors.lastname: Dubois
authors.affiliation: MGX-Montpellier GenomiX, c/o Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, F-34094 Montpellier Cedex 5, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Parrinello
authors.affiliation: Laboratory of Bioinformatics and Systems Biology, Centre of New Technologies, University of Warsaw, Zwirki i Wigury 93, 02-089 Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Skrzypczak
authors.affiliation: Laboratory of Bioinformatics and Systems Biology, Centre of New Technologies, University of Warsaw, Zwirki i Wigury 93, 02-089 Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Ginalski
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier, France; Equipe Labellisée Ligue Contre le Cancer, 14 rue Corvisart, 75013 Paris, France. Electronic address: alengron@igh.cnrs.fr.
authors.forename: Armelle
authors.initials: A
authors.lastname: Lengronne
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, 141 rue de la Cardonille, 34396 Montpellier, France; Equipe Labellisée Ligue Contre le Cancer, 14 rue Corvisart, 75013 Paris, France. Electronic address: ppasero@igh.cnrs.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pasero
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D017353:Gene Deletion; D006655:Histone Deacetylases / Q000378:metabolism*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism*; D056565:Sirtuin 2 / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004275:DNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D064447:Checkpoint Kinase 2; C067022:RAD53 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D006655:Histone Deacetylases