The basidiomycetous fungus Cryptococcus has been known as radiation resistant fungi and is found in highly radioactive environments such as the damaged nuclear reactor at Chernobyl. Although Cryptococcus exhibits greater resistant for gamma radiation than the model yeast Saccharomyces cerevisiae, the resistant mechanism of gamma radiation remains elusive. To elucidate a unique regulatory system for radiation-resistance in C. neoformans, we performed genome-wide comparative analysis through DNA microarray analysis using C. neoformans WT strain (serotype A, H99 strain) responding gamma radiation. Based on the transcriptome analysis, genes involved in DNA damage repair systems (RAD51, RDH54, and RAD54) were significantly increased in response to gamma radiation. Actually, rad54? and rdh54? mutants exhibited sensitivity against both gamma radiation and DNA damage inducers. Furthermore, genes regarding to molecular chaperone and ubiquitination systems were strongly induced. In contrast, expression levels of genes related to protein synthesis, fatty acids/sterols synthesis, and other cellular molecules. Especially, ergosterol homeostasis is required for gamma radiation resistance. Furthermore, radiation-induced genes such as RIG4, RIG5, and RIG6 in C. neoformans play critical roles in gamma radiation resistance. Taken together, the transcriptome analysis contributes to understanding unique molecular mechanism of radiation-resistant fungus C. neoformans. To elucidate transcriptome change during recovery process post irrdiation, samples were taken at three time interval (30 min, 60 min, and 120 min). The three independent DNA microarry with three independent biological replicates were analyzed to obtain high reliability.