Yeast DNA polymerase epsilon participates in leading-strand DNA replication.
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.
Pursell
Zachary F
ZF
Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
Isoz
Isabelle
I
Lundström
Else-Britt
EB
Johansson
Erik
E
Kunkel
Thomas A
TA
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
D004271:DNA, Fungal; D005656:Fungal Proteins; D004257:DNA Polymerase II