An updated perspective on the polymerase division of labor during eukaryotic DNA replication

In eukaryotes three DNA polymerases (Pols), alpha, delta, and epsilon, are tasked with bulk DNA synthesis of nascent strands during genome duplication. Most evidence supports a model where Pol alpha initiates DNA synthesis before Pol epsilon and Pol delta replicate the leading and lagging strands, respectively. However, a number of recent reports, enabled by advances in biochemical and genetic techniques, have highlighted emerging roles for Pol delta in all stages of leading-strand synthesis; initiation, elongation, and termination, as well as fork restart. By focusing on these studies, this review provides an updated perspective on the division of labor between the replicative polymerases during DNA replication.