Epsilonpolymeraasit

Epsilonpolymeraasit, commonly called polymerase epsilon (Pol ε), are a family of high-fidelity DNA polymerases that play a central role in DNA replication in eukaryotes. In prokaryotic contexts, the term can be confused with the epsilon subunit of DNA polymerase III (the proofreading unit, not a separate polymerase), so clear distinctions are important: in bacteria the epsilon subunit provides proofreading activity, whereas in eukaryotes Pol ε is a multi-subunit polymerase complex.

In eukaryotes, Pol ε is a holoenzyme composed of a catalytic subunit and several accessory subunits. The catalytic subunit (POLE) carries the DNA synthesis activity and, in many species, retains a 3′ to 5′ exonuclease proofreading domain that contributes to replication fidelity. Accessory subunits (such as POLE2 and yeast equivalents like Dpb2, Dpb3, and Dpb4 in some organisms) help stabilize the complex and regulate activity. The exact subunit composition varies among organisms.

Functionally, Pol ε primarily synthesizes the leading strand during DNA replication and interacts with other replication machinery, including the CMG helicase complex and PCNA sliding clamp, to coordinate synthesis with lagging-strand processes and checkpoint responses. Its proofreading activity reduces misincorporation, supporting high genomic fidelity.

Clinical relevance arises from mutations in POLE that disrupt proofreading, producing hypermutable tumors and a condition known as polymerase proofreading-associated polyposis (PPAP), which increases the risk of colorectal and other cancers. Pol ε defects are also linked to various cancer subtypes and influence responses to certain therapies, including immune checkpoint inhibitors in some cases.

Origins and evolution of Pol ε show broad conservation from archaea to higher eukaryotes, underscoring its essential role in genome maintenance and faithful DNA replication.