# A Comparative Study for the Incorporation of 8-oxo-dATP in DNA by Human DNA Polymerases

## TL;DR

This study compares how different human DNA polymerases handle the incorporation of a damaged DNA building block called 8-oxo-dATP.

## Contribution

The study reveals distinct abilities of human DNA polymerases to discriminate against 8-oxo-dATP, highlighting Pol λ's poor performance and Pol η's high accuracy.

## Key findings

- Pol λ showed the worst discrimination against 8-oxo-dATP opposite template T.
- Pol η demonstrated the most effective discrimination against 8-oxo-dATP on templates T and G.
- High-fidelity Pol ε (exo-) incorporated 8-oxo-dATP more efficiently than error-prone polymerases.

## Abstract

In this work, we analyzed the ability to incorporate 8-oxo-dATP by several human DNA polymerases: replicative Pol ε (exo-) from Family B; base excision repair (BER) enzymes Pol β and Pol λ from Family X; and translesion Pol η, Pol ι, and Pol κ from Family Y. We demonstrated that human DNA polymerases differ in their abilities to discriminate against 8-oxo-dATP. Among the tested DNA polymerases, Pol λ exhibited the worst ability to discriminate against 8-oxo-dATP opposite template T on DNA substrates with a protruding single-stranded 5′-end and a double-stranded DNA with a 1 nt gap. Pol β and DNA polymerases of Family Y showed relatively high accuracy. Pol η demonstrated the most effective discrimination against 8-oxo-dATP on templates T and G. Pol ι exclusively incorporated 8-oxo-dATP opposite template G but not T. Unexpectedly, the catalytic subunit of high-fidelity Pol ε (exo-) incorporated 8-oxo-dATP opposite templates T and G with higher efficiency compared with the error-prone polymerases of Family Y and Pol β. While the structures of human polymerases with incoming 8-oxo-dATP are not available, we speculate on a possible mechanism of 8-oxo-dATP discrimination.