Nucleotide excision repair (NER) is a conserved DNA repair pathway that enables the repair of chemically and structurally distinct DNA lesions. In prokaryotes, the UvrA, UvrB and UvrC proteins mediate NER in a multistep, ATP-dependent reaction. UvrC catalyses the first incision on the fourth or fifth phosphodiester bond 3' and on the eighth phosphodiester bond 5' from the damage that is to be excised. UvrC proteins contain conserved regions: the GIY-YIG domain, the cys-rich region, the UvrBC domain which interacts with uvrB, the RNAse H endonuclease domain and the Helix hairpin Helix (HhH)2 domain.

This superfamily entry represents the RNAse H endonuclease domain, located at the C-terminus, between the UvrBC and the (HhH)2 domains, nearby the N-terminus of the HhH. Despite the lack of sequence homology, the endonuclease domain has an RNase H-like fold, which is characteristic of enzymes with nuclease or polynucleotide transferase activities. RNase H-related enzymes typically contain a highly conserved carboxylate triad, usually DDE, in their catalytic centre. However, instead of a third carboxylate, UvrC of Thermotoga maritima was found to contain a highly conserved histidine (H488) on helix-4 in close proximity to two aspartates.

DOI:10.1038/sj.emboj.7601497, PFAM:PF08459, INTERPRO:IPR001162