title: Genome-wide model for the normal eukaryotic DNA replication fork.
abstract: To investigate DNA replication enzymology across the nuclear genome of budding yeast, deep sequencing was used to establish the pattern of uncorrected replication errors generated by an asymmetric mutator variant of DNA polymerase δ (Pol δ). Sequencing of 16 genomes identified 1,206-bp substitutions generated over 33 generations by L612M Pol δ in a mismatch repair defective strain. Alignment of sequences flanking these substitutions identified "hotspot" motifs for Pol δ replication errors. The substitutions were distributed evenly across all 16 chromosomes. The vast majority were transitions that occurred with a strand bias that varied in a predictable manner relative to known functional origins of replication. This strand bias strongly supports the idea that Pol δ is primarily a lagging strand polymerase during replication across the entire nuclear genome.
authors.affiliation: Laboratory of Molecular Genetics and Laboratory of Structural Biology, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Andres A
authors.initials: AA
authors.lastname: Larrea
authors.forename: Scott A
authors.initials: SA
authors.lastname: Lujan
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Nick McElhinny
authors.forename: Piotr A
authors.initials: PA
authors.lastname: Mieczkowski
authors.forename: Michael A
authors.initials: MA
authors.lastname: Resnick
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Gordenin
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
mesh_terms: D020137:Base Pair Mismatch / Q000235:genetics; D001483:Base Sequence; D004258:DNA Polymerase III / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics* / Q000502:physiology; D015723:Gene Library; D016681:Genome, Fungal / Q000235:genetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018741:Replication Origin / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D004258:DNA Polymerase III