Both DNA Polymerases δ and ε Contact Active and Stalled Replication Forks differently

Three DNA polymerases (Pol α, Pol δ, and Pol ε) are responsible for eukaryotic genome duplication. When DNA replication stress is encountered, DNA synthesis stalls until the stress is ameliorated. However, it is not known whether there is a difference in the association of each polymerase with active and stalled replication forks. Here, we show that each DNA polymerase has distinct patterns of association with active and stalled replication forks. Pol α is enriched at extending Okazaki fragments of active and stalled forks. In contrast, although Pol δ contacts the nascent lagging strands of active and stalled forks, it binds to only the matured (and not elongating) Okazaki fragments of stalled forks. Pol ε has a greater contact with the nascent ssDNA of leading strand on active forks compared with stalled forks. We propose that the configuration of DNA polymerases at stalled forks facilitate resumption of DNA synthesis after stress removal.