Journal
EMBO REPORTS
Volume 11, Issue 9, Pages 698-704Publisher
WILEY
DOI: 10.1038/embor.2010.112
Keywords
CTP synthetase; molecular combing; replication dynamics; thymidylate synthase; trichostatin A
Categories
Funding
- Association pour la Recherche sur le Cancer
- La Ligue Nationale contre le Cancer
- Agence Nationale de la Recherche
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In eukaryotes, only a fraction of replication origins fire at each S phase. Local histone acetylation was proposed to control firing efficiency of origins, but conflicting results were obtained. We report that local histone acetylation does not reflect origin efficiencies along the adenosine monophosphate deaminase 2 locus in mammalian fibroblasts. Reciprocally, modulation of origin efficiency does not affect acetylation. However, treatment with a deacetylase inhibitor changes the initiation pattern. We demonstrate that this treatment alters pyrimidine biosynthesis and decreases fork speed, which recruits latent origins. Our findings reconcile results that seemed inconsistent and reveal an unsuspected effect of deacetylase inhibitors on replication dynamics.
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