Polymerase Dynamics at the Eukaryotic DNA Replication Fork

This review discusses recent insights in the roles of DNA polymerases (Pol) δ and ∊ in eukaryotic DNA replication. A growing body of evidence specifies Pol ∊ as the leading strand DNA polymerase and Pol δ as the lagging strand polymerase during undisturbed DNA replication. New evidence supporting this model comes from the use of polymerase mutants that show an asymmetric mutator phenotype for certain mispairs, allowing an unambiguous strand assignment for these enzymes. On the lagging strand, Pol δ corrects errors made by Pol α during Okazaki fragment initiation. During Okazaki fragment maturation, the extent of strand displacement synthesis by Pol δ determines whether maturation proceeds by the short or long flap processing pathway. In the more common short flap pathway, Pol δ coordinates with the flap endonuclease FEN1 to degrade initiator RNA, whereas in the long flap pathway, RNA removal is initiated by the Dna2 nuclease/helicase.