1. Nucleotide supply, not local histone acetylation, sets replication origin usage in transcribed regions.
- Author
-
Gay S, Lachages AM, Millot GA, Courbet S, Letessier A, Debatisse M, and Brison O
- Subjects
- Acetylation, Animals, Cells, Cultured, Fibroblasts cytology, Fibroblasts physiology, Histone Deacetylase Inhibitors metabolism, Histone Deacetylases metabolism, Humans, Hydroxamic Acids metabolism, Transcription, Genetic, DNA Replication, Histones metabolism, Nucleotides metabolism, Replication Origin
- Abstract
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.
- Published
- 2010
- Full Text
- View/download PDF