User:Quasihuman/Proofreading (biology)

DNA polymerases
In DNA replication in eukaryotes, DNA synthesis is initiated by DNA polymerase alpha (Pol α), and extended by DNA polymerase delta (Pol δ) and DNA Polymerase epsilon (Pol ɛ). Pol δ and Pol ɛ do the majority of the replication, and are therefore adapted to have a higher fidelity. While the fidelity of most DNA polymerases, such as Pol α, is dependent on base pairing alone, both Pol δ and Pol ɛ have exonuclease domains, which allow for a proofreading function.

In mouse models, mutations in the exonuclease domains of the Pol δ subunit POLD1 and the Pol ɛ subunit POLE develop various cancer phenotypes, such as histiocytic sarcomas, nodal lymphomas, and thymic lymphomas. In humans, rare variations in POLD1 and POLE proofreading function are linked to colorectal cancer.

There is evidence that the exonuclease proofreading activity of a DNA polymerase is disadvantageous when it comes to repairing lesions in DNA.