We propose to study the nature of human chromosomal diseases which have predisposition to cancer. These diseases include Ataxia telangiesctasia, Bloom's syndrome, Fanconi's anemia, incontenenti pigmenti, and Xeroderma pigmentosum. Our hypothesis is that deficiency in DNA repair is an underlying cause; each disease may have a different but related defect. We propose to approach this problem in two parallel ways. Directly, we propose to analyze activities of correctional incision and excision enzymes that may be related to DNA repair in cultured cells derived from these patients. Indirectly, we propose to induce specific repair deficient mutants in cultured Chinese hamster ovary cells and use them to assay and map the defective genes in humans. We propose to examine more closely two series of the many steps in DNA repair: one, single-stranded DNA scission and processes leading to its reunion, and two, excision of defined lesions from DNA. Our objective is to elucidate mechanisms by which a cell maintains its chromosomal integrity and to use this information to help design experiments to answer the question whether repair deficiency in humans leads to cancer.
NIH ExPorter
NIH ExPorter