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Division of labor at the eukaryotic replication fork.

DNA polymerase delta (Pol delta) and DNA polymerase epsilon (Pol epsilon) are both required for efficient replication of the nuclear genome, yet the division of labor between these enzymes has remained unclear for many years. Here we investigate the contribution of Pol delta to replication of the leading and lagging strand templates in Saccharomyces cerevisiae using a mutant Pol delta allele (pol3-L612M) whose error rate is higher for one mismatch (e.g., T x dGTP) than for its complement (A x dCTP). We find that strand-specific mutation rates strongly depend on the orientation of a reporter gene relative to an adjacent replication origin, in a manner implying that >90% of Pol delta replication is performed using the lagging strand template. When combined with recent evidence implicating Pol epsilon in leading strand replication, these data support a model of the replication fork wherein the leading and lagging strand templates are primarily copied by Pol epsilon and Pol delta, respectively.

Pubmed ID: 18439893


  • Nick McElhinny SA
  • Gordenin DA
  • Stith CM
  • Burgers PM
  • Kunkel TA


Molecular cell

Publication Data

April 25, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM32431
  • Agency: NIGMS NIH HHS, Id: R01 GM032431
  • Agency: Intramural NIH HHS, Id: Z01 ES065070-17

Mesh Terms

  • Alleles
  • DNA Mismatch Repair
  • DNA Mutational Analysis
  • DNA Polymerase II
  • DNA Polymerase III
  • DNA Replication
  • Genes, Reporter
  • Models, Biological
  • MutS Homolog 2 Protein
  • Mutation
  • Replication Origin
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins