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Efficient interstrand crosslink (ICL) repair in yeast depends on the Pso2/Snm1 protein. Pso2 is a member of the highly conserved metallo-β-lactamase structural family of nucleases. Mammalian cells possess three SNM1/Pso2 related proteins, SNM1A, SNM1B/Apollo, and SNM1C/Artemis. Evidence that SNM1A and SNM1B contribute to ICL repair is mounting, whereas Artemis appears to primarily contribute to non-ICL repair pathways, particularly some double-strand break repair events. Yeast Pso2 and all three mammalian SNM1-family proteins have been shown to possess nuclease activity. Here, we review the biochemical, genetic, and cellular evidence for the SNM1 family as DNA repair factors, focusing on ICL repair. Environ. Mol. Mutagen. 51:635-645, 2010.