A Major Role of DNA Polymerase δ in Replication of Both the Leading and Lagging DNA Strands

Mol Cell. 2015 Jul 16;59(2):163-175. doi: 10.1016/j.molcel.2015.05.038. Epub 2015 Jul 2.


Genetic studies with S. cerevisiae Polδ (pol3-L612M) and Polε (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that Polε is the primary leading strand replicase and that Polδ is restricted to replicating the lagging strand template. Contrary to this widely accepted view, here we show that Polδ plays a major role in the replication of both DNA strands, and that the paucity of pol3-L612M-generated errors on the leading strand results from their more proficient removal. Thus, the apparent lack of Polδ contribution to leading strand replication is due to differential mismatch removal rather than differential mismatch generation. Altogether, our genetic studies with Pol3 and Pol2 mutator alleles support the conclusion that Polδ, and not Polε, is the major DNA polymerase for carrying out both leading and lagging DNA synthesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Substitution
  • Base Pair Mismatch
  • DNA Polymerase II / genetics
  • DNA Polymerase II / metabolism
  • DNA Polymerase III / genetics
  • DNA Polymerase III / metabolism*
  • DNA Replication*
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism*
  • Exodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / metabolism
  • Genome, Fungal
  • Mutagenesis, Site-Directed
  • Mutation
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • DNA, Fungal
  • POL3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • URA3 protein, S cerevisiae
  • DNA Polymerase II
  • DNA Polymerase III
  • Exodeoxyribonucleases
  • exodeoxyribonuclease I