Journal
GENES & DEVELOPMENT
Volume 16, Issue 19, Pages 2479-2484Publisher
COLD SPRING HARBOR LAB PRESS
DOI: 10.1101/gad.232902
Keywords
DNA replication; DNA combing; Sir2; recombination; aging
Categories
Funding
- NCI NIH HHS [R21CA81721] Funding Source: Medline
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How eukaryotes specify their replication origins is an important unanswered question. Here, we analyze the replicative organization of yeast rDNA, which consists of -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 sir2Delta 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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