Dynamics of enzymatic interactions during short flap human Okazaki fragment processing by two forms of human DNA polymerase δ.

•Two forms of human Pol δ were characterized in a reconstituted system.•Pol δ4 exhibits strong strand displacement activity in contrast to Pol δ3.•Primary cleavage products in the coupled Pol δ/Fen1 reactions were mononucleotides.•Pol δ3 exhibits near-ideal properties for a role in Okazaki fragment processing.•These studies support the novel concept that Pol δ3 participates in DNA replication.