XPC and skin cancer: While our analysis suggests that elimination of GG-NER in yeast enhances mutation frequency in late-replicating regions, previous studies in human skin cancers indicate that loss of GG-NER (e.g., in XPC-/- skin cancers) reduces the enrichment of mutations in late-replicating regions [16,17], likely because late-replicating regions in human cells are largely heterochromatic and, therefore, normally inaccessible to the GG-NER machinery.