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PMID: 12368258 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Genes & development ·Vol. 16 ·No. 19 ·2002-10-01 ·Pages 2479-84

Pasero P, Bensimon A, Schwob E

Abstract

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.

MeSH Terms
DNA Replication DNA, Fungal/biosynthesis DNA, Ribosomal/biosynthesis Histone Deacetylases/genetics,physiology Repetitive Sequences, Nucleic Acid Replication Origin Saccharomyces cerevisiae/genetics,physiology Silent Information Regulator Proteins, Saccharomyces cerevisiae/genetics,physiology Sirtuin 2 Sirtuins/genetics,physiology
Chemicals
DNA, Fungal DNA, Ribosomal Silent Information Regulator Proteins, Saccharomyces cerevisiae SIR2 protein, S cerevisiae Sirtuin 2 Sirtuins Histone Deacetylases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pasero Philippe
Institute of Molecular Genetics, CNRS UMR 5535 and Université Montpellier II, 34293 Montpellier cedex 5, France.
Bensimon Aaron
Schwob Etienne
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.232902
Published
2002-10-01
Pages
2479-84
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC187456
Subset
IM
Grants
NCI NIH HHS · R21CA81721 · United States
Corrections
CommentIn
PMID: 12368256
External Links
PubMed source DOI: 10.1101/gad.232902 PMC Full Text View journal details
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