title: Nucleotide supply, not local histone acetylation, sets replication origin usage in transcribed regions.
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.
authors.affiliation: Institut Curie, Centre de Recherche, 26 rue d'Ulm, 75248 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gay
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lachages
authors.forename: Gael A
authors.initials: GA
authors.lastname: Millot
authors.forename: Sylvain
authors.initials: S
authors.lastname: Courbet
authors.forename: Anne
authors.initials: A
authors.lastname: Letessier
authors.forename: Michelle
authors.initials: M
authors.lastname: Debatisse
authors.forename: Olivier
authors.initials: O
authors.lastname: Brison
mesh_terms: D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism*; D018741:Replication Origin; D014158:Transcription, Genetic
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D009711:Nucleotides; C012589:trichostatin A; D006655:Histone Deacetylases