CO2 Protects Cells from Iron-Fenton Oxidative DNA Damage in E. coli and Humans

Whereas hydroxyl radical is commonly named as the Fenton product responsible for DNA and RNAdamage in cells, here we demonstrate that the cellular reaction generates carbonate radicalanion due to physiological levels of bicarbonate. Analysis of the metabolome, the transcriptome,and the human genome shows a consistent buffering of H2O2-induced oxidativestress 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 withglycosylase-dependent qPCR studies of oxidative DNA damage in telomeres. The focusing of oxidativemodification on one pathway is consistent with the highly evolved base excision repair suite of enzymesand their involvement in gene regulation in response to oxidative stress.