title: Heterogeneity of DNA repair at the gene level.
abstract: Overall genomic DNA repair efficiencies do not necessarily correlate with cellular sensitivities to radiation and other DNA-damaging agents. My colleagues and I have developed experimental approaches to measure DNA lesions and their repair in defined DNA sequences and we have discovered that for some types of damage, such as the cyclobutane pyrimidine dimers produced in DNA by ultraviolet light (UV), repair is highly selective for transcribed DNA strands in active genes: repair may be directly coupled to the transcription apparatus. Freely diffusing repair complexes may account for the much lower repair efficiencies observed in silent genomic domains. The viability of mammalian cells may be ensured through selective repair of transcription-blocking DNA damage in essential, expressed genes rather than as a consequence of overall genomic repair. Persisting damage in non-transcribed domains may account for some cell-specific mutagenic and carcinogenic phenomena. In UV-irradiated cells from xeroderma pigmentosum (complementation group C) there is a deficiency in the removal of pyrimidine dimers from silent genomic domains, while in Cockayne's syndrome the defect appears to involve the preferential repair of active genes. In contrast to the cancer-prone characteristic of xeroderma pigmentosum the victims of Cockayne's syndrome do not suffer enhanced skin cancer induction by sunlight. Susceptibility to cancer and other biological endpoints is clearly dependent upon the fine structure detail of the DNA repair response.
authors.affiliation: Department of Biological Sciences, Stanford University, CA 94305-5020.
authors.forename: P C
authors.initials: PC
authors.lastname: Hanawalt
mesh_terms: D000818:Animals; D004249:DNA Damage; D015342:DNA Probes; D004260:DNA Repair; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D011519:Proto-Oncogenes / Q000187:drug effects / Q000235:genetics; D011740:Pyrimidine Dimers / Q000235:genetics
chemical_list: D015342:DNA Probes; D011740:Pyrimidine Dimers