The Histone Deacetylases Sir2 and Rpd3 Act on Ribosomal DNA to Control the Replication Program in Budding Yeast

Kazumasa Yoshida, Julien Bacal, Damien Desmarais, Ismaël Padioleau, Olga Tsaponina, Andrei Chabes, Véronique Pantesco, Emeric Dubois, Hugues Parrinello, Magdalena Skrzypczak, Krzysztof Ginalski, Armelle Lengronne, Philippe Pasero

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)691-697
Number of pages7
JournalMolecular Cell
Volume54
Issue number4
DOIs
Publication statusPublished - May 22 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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