DNA Polymerase ε: A Polymerase of Unusual Size (and Complexity)

Abstract

Publisher Summary DNA polymerase epsilon (Pol epsilon) is a large, multi-subunit polymerase that is conserved throughout all eukaryotes. In addition to its role as one of the three DNA polymerases responsible for bulk chromosomal replication, Pol epsilon is implicated in a wide variety of important cellular processes, including the repair of damaged DNA, DNA recombination, and the regulation of proper cell cycle progression. Pol e catalyzes DNA template-dependent DNA synthesis by a phosphoryl transfer reaction involving nucleophilic attack by the 30 hydroxyl of the primer terminus on the a-phosphate of the incoming deoxynucleoside triphosphate (dNTP). The products of this reaction are pyrophosphate and a DNA chain increased in length by one nucleotide. The catalytic mechanism is conserved among DNA polymerases. It begins with binding of a primer template to the polymerase. Like all polymerases, Pol e ultimately does not generate all types of errors at equal rates, but rather has distinctive error specificity. Two features of Pol e error specificity are particularly interesting in light of its proposed biological roles in DNA replication. One is that Pol e is among the most accurate of DNA polymerases for single base deletion/insertion errors. Because indels are typically generated more frequently within repetitive sequences, this property may be relevant to the proposal that Pol e has a particularly important role in replicating heterochromatic DNA, which is enriched in repetitive sequences. Another is that a mutant derivative of Pol e has a unique base substitution error specificity that has been useful for inferring its role in replication of the leading strand template.