title: Yeast DNA polymerase epsilon participates in leading-strand DNA replication.
abstract: Multiple DNA polymerases participate in replicating the leading and lagging strands of the eukaryotic nuclear genome. Although 50 years have passed since the first DNA polymerase was discovered, the identity of the major polymerase used for leading-strand replication is uncertain. We constructed a derivative of yeast DNA polymerase epsilon that retains high replication activity but has strongly reduced replication fidelity, particularly for thymine-deoxythymidine 5'-monophosphate (T-dTMP) but not adenine-deoxyadenosine 5'-monophosphate (A-dAMP) mismatches. Yeast strains with this DNA polymerase epsilon allele have elevated rates of T to A substitution mutations. The position and rate of these substitutions depend on the orientation of the mutational reporter and its location relative to origins of DNA replication and reveal a pattern indicating that DNA polymerase epsilon participates in leading-strand DNA replication.
authors.affiliation: Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
authors.forename: Zachary F
authors.initials: ZF
authors.lastname: Pursell
authors.forename: Isabelle
authors.initials: I
authors.lastname: Isoz
authors.forename: Else-Britt
authors.initials: EB
authors.lastname: Lundström
authors.forename: Erik
authors.initials: E
authors.lastname: Johansson
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
mesh_terms: D020137:Base Pair Mismatch; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004271:DNA, Fungal / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics; D009154:Mutation; D017354:Point Mutation; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D004257:DNA Polymerase II