An orchestra of survival: Molecular mechanisms of radiation resistance across extremophiles

An orchestra of molecular mechanisms endows radiation-resistant extremophiles with extraordinary survival capabilities under extreme ionizing radiation. This review systematically explores the arsenal of key molecular strategies underpinning extreme radioresistance, including efficient DNA damage response and repair pathways, robust reactive oxygen species (ROS) scavenging systems, specialized protective proteins (e.g., Dsup, PprI), and coordinated regulatory networks. This review extensively examines species-specific adaptations in a diverse range of radioresistant organisms, such as Deinococcus radiodurans , archaea, lichens, bdelloid rotifers, Drosophila melanogaster, cockroaches, Caenorhabditis elegans , and tardigrades. Despite the conservation of core mechanisms such as DNA repair machinery, significant interspecies variations exist in antioxidant defense systems and cellular structure remodeling strategies. Based on the available data, this review further conducts an analysis of convergent vs. divergent evolution and quantitative efficiency metrics across species. Finally, translational applications of these mechanisms in radiobiology, medicine and space science are discussed, with future research directions highlighted that aim to exploit these natural radioprotective systems for technological and therapeutic innovations.