Studies in this laboratory are designed to elucidate the role of DNA repair processes in carcinogenesis and in normal and abnormal aging and in neurodegeneration. Most studies have been conducted with cells from patients with xeroderma pigmentosum (XP), who have defective DNA repair plus multiple cutaneous malignancies and premature aging of sun-exposed skin and of the nervous system. Cells from patients with primary neuronal, muscular, and retinal degenerations are also being studied. These diseases include ataxia telangiectasia, Alzheimer disease, Parkinson disease, Huntington disease, Duchenne muscular dystrophy, retinitis pigmentosa, Friedreich ataxia, and Cockayne syndrome (CS). These studies are designed to elucidate the pathogenesis of these disorders. We assess the biological effectiveness of DNA repair by 1) in vitro assays of cell survival after treatment of the cells with DNA-damaging agents; 2) analysis of chromosome and chromatid aberrations in cells treated with DNA-damaging agents; and 3) transfection studies using irradiated plasmids. We search for DNA damage by 1) extracting the DNA and having it subjected to analysis by capillary gas chromatography-mass spectrometry; and 2) studying unscheduled DNA synthesis induced in cultured cells by chemical carcinogens. We search in patient cells for abnormalities in DNA- repair genes and in their DNA-damage inducible transcripts using cDNA probes in Southern and Northern blot hybridization studies.
