Nucleotide supply, not local histone acetylation, sets replication origin usage in transcribed regions

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 monopho...

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Bibliographic Details
Published in:EMBO reports 2010-09, Vol.11 (9), p.698-704
Main Authors: Gay, Sophie, Lachages, Anne-Marie, Millot, Gael A, Courbet, Sylvain, Letessier, Anne, Debatisse, Michelle, Brison, Olivier
Format: Article
Language:English
Subjects:
Acetylation
Adenosine
Animals
Biosynthesis
Cells, Cultured
CTP synthetase
DNA Replication
EMBO09
EMBO13
Fibroblasts - cytology
Fibroblasts - physiology
Histone Deacetylase Inhibitors - metabolism
Histone Deacetylases - metabolism
Histones - metabolism
Humans
Hydroxamic Acids - metabolism
Inhibitor drugs
Mammals
Molecular biology
molecular combing
Nucleotides - metabolism
replication dynamics
Replication Origin
Scientific Report
Scientific Reports
thymidylate synthase
Transcription, Genetic
trichostatin A
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Summary: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. Replication origin usage is not determined by local histone acetylation levels, but by the availability of nucleotides, which is modified following forced alterations of protein acetylation balance in the cell.
ISSN:1469-221X
1469-3178
DOI:10.1038/embor.2010.112