Abstract
Several studies in the past decade support a model wherein DNA polymerase e (Pol e) carries out the majority of leading-strand DNA replication of the undamaged eukaryotic nuclear genome. Now a recent paper in Molecular Cell from the Prakash laboratory challenges this model, claiming instead that Pol δ is the major replicase for both strands and that Pol e’s primary role is only to proofread errors made by Pol δ during leading-strand replication (Johnson et al., 2015). While we fully subscribe to the idea that the replication fork is plastic and that its composition can adapt to various challenges, we believe the foundation for an unchallenged replication fork remains as established before the Prakash paper, for the following reasons.
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