Protein persulfidation identified as key component in DNA damage response

Research published in Free Radical Biology and Medicine indicates that protein persulfidation is a conserved component of the cellular redox response to DNA damage. By studying Saccharomyces cerevisiae exposed to methyl methanesulfonate (MMS), researchers identified that the activation of the DNA damage response (DDR) is accompanied by rapid redox changes, even without a generalized oxidative stress response.

MMS exposure leads to a selective remodeling of cysteine oxidative modifications, specifically characterized by a robust induction of protein persulfidation and a decrease in free thiols. These changes are linked to increased intracellular hydrogen sulfide levels, suggesting that reactive sulfur species play a functional role in the cellular response to genotoxic stress. Proteome-wide analyses show these modifications preferentially target proteins involved in genome maintenance, nucleotide biosynthesis, and central metabolism. This process appears to facilitate metabolic adaptation, including increased mitochondrial respiration and ATP production.