Unraveling the mechanisms of extreme radioresistance in prokaryotes: Lessons from nature

[Display omitted] The last 50 years, a variety of archaea and bacteria able to withstand extremely high doses of ionizing radiation, have been discovered. Several lines of evidence suggest a variety of mechanisms explaining the extreme radioresistance of microorganisms found usually in isolated environments on Earth. These findings are discussed thoroughly in this study. Although none of the strategies discussed here, appear to be universal against ionizing radiation, a general trend was found. There are two cellular mechanisms by which radioresistance is achieved: (a) protection of the proteome and DNA from damage induced by ionizing radiation and (b) recruitment of advanced and highly sophisticated DNA repair mechanisms, in order to reconstruct a fully functional genome. In this review, we critically discuss various protecting (antioxidant enzymes, presence or absence of certain elements, high metal ion or salt concentration etc.) and repair (Homologous Recombination, Single-Strand Annealing, Extended Synthesis-Dependent Strand Annealing) mechanisms that have been proposed to account for the extraordinary abilities of radioresistant organisms and the homologous radioresistance signature genes in these organisms. In addition, and based on structural comparative analysis of major radioresistant organisms, we suggest future directions and how humans could innately improve their resistance to radiation-induced toxicity, based on this knowledge.