Nucleotide Excision Repair: Variations Associated with Cancer Development and Speciation J E CLEAVER1 • .I R SPEAKMAN2. J PG VOLPE1 1Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, California 94143-0750; 2Depart17lent ofZnology, University of Aberdeen, Aberdeen AB92TN Introduction Mechanism of nucleotide excision repair The coupling of transcription with repair Diseases of nucleotide excision repair Xeroderma pigmentosum Cockayne syndrome Trichothiodystrophy Interindividual variability of nucleotide excision DNA excision repair and speciation Implications for cancer and other health effects Summary The genome of cells presents massive problems of fidelity and maintenance of accurate information (Lindahl, 1993). A diploid human cell has 1.3 X 10 10 bases that must be faithfully maintained, replicated and passed on to the daughter cells. Given the large number of endogenous and exogenous genotoxic agents that cells encounter during the lifetime of their host, it is not surprising that such hosts have evolved elaborate means of safeguarding their genomes. Although preventive mechanisms are by no means trivial (eg anti- oxidants), DNA repair is probably the most important mechanism a cell has to maintain its genome faithfully. Major roles for repair systems have been recog- nized in mending endogenous oxidative damage in nuclear and mitochondrial DNA, in correcting DNA mismatches associated with non-polyposis colon can- cer, in immunodeficiencies, in skin carcinogenesis in xeroderma pigmentosum (XP) and in developmental and neurological abnormalities in XP, Cockayne syndrome (CS) and trichothiodystrophy (TTD) (Cleaver and Kraemer, 1989). Less obvious, but possibly equally important, are variations in repair between individuals and between species. Cancer Surveys Volume 25: Genetics and Cancer: A Second Look © 1995 Imperial Cancer Research Fund. 0-87969-469-6/95. $5.00 + .00 125