DNA Polymerases Divide the Labor of Genome Replication

Trends Cell Biol. 2016 Sep;26(9):640-654. doi: 10.1016/j.tcb.2016.04.012. Epub 2016 Jun 1.


DNA polymerases synthesize DNA in only one direction, but large genomes require RNA priming and bidirectional replication from internal origins. We review here the physical, chemical, and evolutionary constraints underlying these requirements. We then consider the roles of the major eukaryotic replicases, DNA polymerases α, δ, and ɛ, in replicating the nuclear genome. Pol α has long been known to extend RNA primers at origins and on Okazaki fragments that give rise to the nascent lagging strand. Taken together, more recent results of mutation and ribonucleotide incorporation mapping, electron microscopy, and immunoprecipitation of nascent DNA now lead to a model wherein Pol ɛ and Pol δ, respectively, synthesize the majority of the nascent leading and lagging strands of undamaged DNA.

Keywords: DNA replication; evolution; genomic ribonucleotide; polymerase; replication fork.

Publication types

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

MeSH terms

  • Animals
  • DNA Replication*
  • DNA-Directed DNA Polymerase / metabolism*
  • Eukaryotic Cells / metabolism
  • Genome*
  • Humans
  • Models, Biological
  • Mutation / genetics


  • DNA-Directed DNA Polymerase