Nucleotide excision repair (NER) was discovered in both prokaryotes and eukaryotes in the 1960s (Friedberg et al., 2005). The process corrects a wide spectrum of damage to DNA bases that results in distortions in the native conformation of DNA, including damage induced by ultraviolet (UV) light and by a plethora of chemicals. NER comprises two distinct subpathways. Global genome repair (GGR) repairs lesions in regions of the genome that are transcriptionally silent, and transcription-coupled repair (TCR) repairs lesions in regions of the genome that are transcriptionally active. A key difference between these two NER pathways is the molecular mechanism used to recognize the damaged base (designated by a red star in the SnapShot figure).