Networked Communication between Polymerase and Exonuclease Active Sites in Human Mitochondrial DNA Polymerase.

ABSTRACT: High fidelity human mitochondrial DNA polymerase (Pol γ) contains two active sites, a DNA polymerization site (pol) and a 3'-5' exonuclease site (exo) for proofreading. Although separated by 35 Å, coordination between the pol and exo sites is crucial to high fidelity replication. The biophysical mechanisms for this coordination are not completely understood. To understand the communication between the two active sites, we used a statistical-mechanical model of the protein ensemble to calculate the energetic landscape and local stability. We compared a series of structures of Pol γ, complexed with primer/template DNA, and either a nucleotide substrate or a series of nucleotide analogues, which are differentially incorporated and excised by pol and exo</

SUBMITTER: Sowers ML 

PROVIDER: S-EPMC7119269 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature