Roles for DNA polymerase δ in initiating and terminating leading strand DNA replication

Nat Commun. 2019 Sep 5;10(1):3992. doi: 10.1038/s41467-019-11995-z.

Abstract

Most current evidence indicates that DNA polymerases ε and δ, respectively, perform the bulk of leading and lagging strand replication of the eukaryotic nuclear genome. Given that ribonucleotide and mismatch incorporation rates by these replicases influence somatic and germline patterns of variation, it is important to understand the details and exceptions to this overall division of labor. Using an improved method to map where these replicases incorporate ribonucleotides during replication, here we present evidence that DNA polymerase δ universally participates in initiating leading strand synthesis and that nascent leading strand synthesis switches from Pol ε to Pol δ during replication termination. Ribonucleotide maps from both the budding and fission yeast reveal conservation of these processes. These observations of replisome dynamics provide important insight into the mechanisms of eukaryotic replication and genome maintenance.

Publication types

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

MeSH terms

  • DNA Polymerase II / metabolism*
  • DNA Polymerase III / genetics
  • DNA Polymerase III / metabolism*
  • DNA Replication / physiology*
  • Eukaryotic Cells / metabolism
  • Genomics
  • Models, Biological
  • Ribonucleotides / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism

Substances

  • Ribonucleotides
  • Saccharomyces cerevisiae Proteins
  • DNA Polymerase II
  • DNA Polymerase III