Human Mitochondrial DNA Polymerase Metal Dependent UV Lesion Bypassing Ability

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2022 Mar 31

PMID 35355510

Authors

Joon Park

Noe Baruch-Torres

Shigenori Iwai

Geoffrey K Herrmann

Luis G Brieba

Y Whitney Yin

Affiliations

Soon will be listed here.

Abstract

Human mitochondrial DNA contains more UV-induced lesions than the nuclear DNA due to lack of mechanism to remove bulky photoproducts. Human DNA polymerase gamma (Pol γ) is the sole DNA replicase in mitochondria, which contains a polymerase () and an exonuclease () active site. Previous studies showed that Pol γ only displays UV lesion bypassing when its exonuclease activity is obliterated. To investigate the reaction environment on Pol γ translesion activity, we tested Pol γ DNA activity in the presence of different metal ions. While Pol γ is unable to replicate through UV lesions on DNA templates in the presence of Mg, it exhibits robust translesion DNA synthesis (TLS) on cyclobutane pyrimidine dimer (CPD)-containing template when Mg was mixed with or completely replaced by Mn. Under these conditions, the efficiency of Pol γ's TLS opposite CPD is near to that on a non-damaged template and is 800-fold higher than that of exonuclease-deficient Pol γ. Interestingly, Pol γ exhibits higher exonuclease activity in the presence of Mn than with Mg, suggesting Mn-stimulated Pol γ TLS is not via suppressing its exonuclease activity. We suggest that Mn ion expands Pol γ's active site relative to Mg so that a UV lesion can be accommodated and blocks the communication between and active sites to execute translesion DNA synthesis.

Citing Articles

Mitochondrial DNA Polymerase POLIB Contains a Novel Polymerase Domain Insertion That Confers Dominant Exonuclease Activity.

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PMID: 36399653 PMC: 9731263. DOI: 10.1021/acs.biochem.2c00392.

Editorial: Nucleic Acid Polymerases: The Two-Metal-Ion Mechanism and Beyond.

Pata J, Yin Y, Lahiri I Front Mol Biosci. 2022; 9:948326.

PMID: 35911968 PMC: 9332193. DOI: 10.3389/fmolb.2022.948326.

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