Across the tree of life, radiation resistance is governed by antioxidant Mn ²⁺ , gauged by paramagnetic resonance

Significance Decades of functional genomic efforts have failed to predict the ability of cells to survive ionizing radiation (IR). Evidence is mounting that small high-symmetry antioxidant complexes of manganous ions with metabolites (H-Mn 2+ ) are responsible for cellular IR resistance, and that H-Mn 2+ protects the proteome, not the genome, from IR-induced reactive oxygen species. We show that the amount of H-Mn 2+ in nonirradiated living cells is readily gauged by electron paramagnetic resonance (EPR) spectroscopy and highly diagnostic of their DNA repair efficiency and survival after gamma-radiation exposure. This spectroscopic measure of cellular H-Mn 2+ content is the strongest known biological indicator of cellular IR resistance between and within organisms across the three domains of the tree of life, with potential applications including optimization of radiotherapy.