TY - JOUR
T1 - The Histone Deacetylases Sir2 and Rpd3 Act on Ribosomal DNA to Control the Replication Program in Budding Yeast
AU - Yoshida, Kazumasa
AU - Bacal, Julien
AU - Desmarais, Damien
AU - Padioleau, Ismaël
AU - Tsaponina, Olga
AU - Chabes, Andrei
AU - Pantesco, Véronique
AU - Dubois, Emeric
AU - Parrinello, Hugues
AU - Skrzypczak, Magdalena
AU - Ginalski, Krzysztof
AU - Lengronne, Armelle
AU - Pasero, Philippe
N1 - Funding Information:
We thank Hiroyuki Araki (National Institute of Genetics, Mishima), Jef Boeke (Johns Hopkins University School of Medicine, Baltimore), Giorgio Camilloni (University of Roma La Sapienza), Michael Grunstein (UCLA, Los Angeles), and Takehiko Kobayashi (National Institute of Genetics, Mishima) for strains and John Diffley for antibodies. We thank Seiji Tanaka (National Institute of Genetics, Mishima) for help with the construction of GALp-3/7/45 strains and Marta Radman-Livaja (IGMM, Montpellier) for help with the MNase-seq experiments. We thank Karlene Cimprich, Susanne Schmidt, Yea-Lih Lin, Benjamin Pardo, and members of the Pasero laboratory for discussions and comments on the manuscript. Work in the Pasero laboratory is supported by the “Agence Nationale pour la Recherche” (ANR), the “Institut National du Cancer” (INCa), and the “Ligue contre le Cancer (équipe labellisée).” A.L. thanks the Région Languedoc-Roussillon (Programme Chercheur d’Avenir) for support. K.Y. was a fellow of the “Ligue contre le Cancer.” Work in the Ginalski lab is supported by Foundation for Polish Science (TEAM) and Polish National Science Centre (2011/02/A/NZ2/00014).
PY - 2014/5/22
Y1 - 2014/5/22
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2014.04.032
DO - 10.1016/j.molcel.2014.04.032
M3 - Article
C2 - 24856221
AN - SCOPUS:84900989853
VL - 54
SP - 691
EP - 697
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 4
ER -