
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.26.609766
preprint
1
Article
CO 2 protects cells from iron-Fenton oxidative DNA damage in E. coli and humans
Fleming Aaron M.
Dingman Justin C.
Burrows Cynthia J.
26 8 2024
2024.08.26.609766https://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.26.609766
nihpp-2024.08.26.609766.pdf
Abstract

Whereas hydroxyl radical is commonly named as the Fenton product responsible for DNA and RNA damage in cells, here we demonstrate that the cellular reaction generates carbonate radical anion due to physiological levels of bicarbonate. Analysis of the metabolome, transcriptome and, in human cells, the nuclear genome shows a consistent buffering of H 2 O 2 -induced oxidative stress leading to one common pathway, namely guanine oxidation. Particularly revealing are nanopore-based studies of direct RNA sequencing of cytosolic and mitochondrial ribosomal RNA along with glycosylase-dependent qPCR studies of oxidative DNA damage in telomeres. The focusing of oxidative modification on one pathway is consistent with the highly evolved base excision repair suite of enzymes and their involvement in gene regulation in response to oxidative stress.
==== Body
pmc
