title: Mutation rates across budding yeast chromosome VI are correlated with replication timing.
abstract: Previous experimental studies suggest that the mutation rate is nonuniform across the yeast genome. To characterize this variation across the genome more precisely, we measured the mutation rate of the URA3 gene integrated at 43 different locations tiled across Chromosome VI. We show that mutation rate varies 6-fold across a single chromosome, that this variation is correlated with replication timing, and we propose a model to explain this variation that relies on the temporal separation of two processes for replicating past damaged DNA: error-free DNA damage tolerance and translesion synthesis. This model is supported by the observation that eliminating translesion synthesis decreases this variation.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Lang
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Murray
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D017931:DNA Primers / Q000235:genetics; D042522:DNA Replication Timing / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D004718:Saccharomycetales / Q000235:genetics*; D013045:Species Specificity
chemical_list: D017931:DNA Primers; D029701:Saccharomyces cerevisiae Proteins; C554167:URA3 protein, S cerevisiae