Single-molecule analysis reveals clustering and epigenetic regulation of replication origins at the yeast rDNA locus

Pasero, P.; Bensimon, A.; Schwob, E.

Genes Dev

2002-10-01 / vol 16 / pages 2479-84


How eukaryotes specify their replication origins is an important unanswered question. Here, we analyze the replicative organization of yeast rDNA, which consists of approximately 150 identical repeats, each containing a potential origin. Using DNA combing and single-molecule imaging, we show that functional rDNA origins are clustered and interspersed with large domains where initiation is silenced. This repression is largely mediated by the Sir2p histone-deacetylase. Increased origin firing in sir2 Delta mutants leads to the accumulation of circular rDNA species, a major determinant of yeast aging. We conclude that rDNA replication is regulated epigenetically and that Sir2p may promote genome stability and longevity by suppressing replication-dependent rDNA recombination.

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IGMM team(s) involved in this publication

*DNA Replication; DNA, Fungal/*biosynthesis; *Repetitive Sequences, Nucleic Acid; *Replication Origin; cerevisiae/genetics/*physiology; DNA, Ribosomal/*biosynthesis; Histone Deacetylases/genetics/*physiology; Saccharomyces cerevisiae/genetics/physiology; Silent Information Regulator Proteins, Saccharomyces; Sirtuins/genetics/*physiology

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