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Trends Cell Biol. 2008 Nov;18(11):521-7. doi: 10.1016/j.tcb.2008.08.005. Epub 2008 Sep 27.

Dividing the workload at a eukaryotic replication fork.

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Laboratory of Molecular Genetics and Laboratory of Structural Biology, 111 T.W. Alexander Drive, National Institute of Environmental Health Sciences, National Institute of Health, DHHS, Research Triangle Park, NC 27709, USA.


Efficient and accurate replication of the eukaryotic nuclear genome requires DNA polymerases (Pols) alpha, delta and epsilon. In all current replication fork models, polymerase alpha initiates replication. However, several models have been proposed for the roles of Pol delta and Pol epsilon in subsequent chain elongation and the division of labor between these two polymerases is still unclear. Here, we revisit this issue, considering recent studies with diagnostic mutator polymerases that support a model wherein Pol epsilon is primarily responsible for copying the leading-strand template and Pol delta is primarily responsible for copying the lagging-strand template. We also review earlier studies in light of this model and then consider prospects for future investigations of possible variations on this simple division of labor.

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