To deal with chemically reactive oxygen molecules constantly threatening aerobic life, cells are readily equipped with elabo-rate biological antioxidant systems. Superoxide dismutase is a metalloenzyme catalytically eliminating superoxide radi-cal as a first-line defense mechanism against oxidative stress. Multiple different SOD isoforms have been developed through-out evolution to play distinct roles in separate subcellular com-partments. SOD is not essential for viability of most aerobic organisms and intriguingly found even in strictly anaerobic bacteria. Sod1 has recently been known to play important roles as a nuclear transcription factor, an RNA binding pro-tein, a synthetic lethal interactor, and a signal modulator in glucose metabolism, most of which are independent of its canonical function as an antioxidant enzyme. In this review, recent advances in understanding the unconventional role of Sod1 are highlighted and discussed with an emphasis on its genetic crosstalk with DNA damage repair/checkpoint path-ways. The budding yeast Saccharomyces cerevisiae has been successfully used as an efficient tool and a model organism to investigate a number of novel functions of Sod1.