DNA interstrand crosslinks are complex lesions that covalently link both strands of the duplex DNA. Lesion removal is proposed to initiate via the UvrABC nucleotide excision repair complex, however less is known about the subsequent steps of this complex repair pathway. In this study, we characterized the contribution of nucleotide excision repair mutants to survival in the presence of psoralen-induced damage. Unexpectedly, we observed that the nucleotide excision repair mutants exhibit differential sensitivity to psoralen-induced damage, with uvrC mutants being less sensitive than either uvrA or uvrB. We show that Cho, an alternative endonuclease, acts with UvrAB and is responsible for the reduced hypersensitivity of uvrC mutants. We find that Cho's contribution to survival correlates with the presence of DNA interstrand crosslinks, rather than monoadducts, and operates at a step after, or independent from, the initial incision during the global repair of psoralen DNA adducts from the genome.