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. [1]
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. [1] In humans, rare variations in POLD1 and POLE proofreading function are linked to colorectal cancer. [2]
There is evidence that the exonuclease proofreading activity of a DNA polymerase is disadvantageous when it comes to repairing lesions in DNA. [3]
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. [1]
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. [1] In humans, rare variations in POLD1 and POLE proofreading function are linked to colorectal cancer. [2]
There is evidence that the exonuclease proofreading activity of a DNA polymerase is disadvantageous when it comes to repairing lesions in DNA. [3]