Transcription-Coupled Repair and Breast Cancer
Abstract
We have studied transcription-coupled repair (TCR) and global genome repair (GGR) of UV damage in the dihydrofolate reductase gene in HCCl937 cells. HCC1937 is a human breast cancer cell line that has mutations in BRCAl. We found no defect in the removal of UV-induced cyclobutane pyrimidine dimers. Hence, we and others find no evidence for a linkage between defects in either BRCAl or BRCA2 and reduced repair of "bulky adducts." We have now focused our attention on the construction of inducible expression systems to regulate DNA repair proteins in different genetic backgrounds. Nucleotide excision repair (NER) is the major pathway in humans for the removal of UV photoproducts. In addition it removes a wide variety of bulky lesions formed by chemical agents including carcinogens. Hence mutations or polymorphisms in NER genes could be associated with an increased risk of breast cancer if a reduction in the removal of carcinogens is involved in the etiology of breast cancer. We have constructed expression vectors containing wild type or polymorphic alleles of the XPA gene and independently introduced them into an XPA deficient cell line. TCR, GGR and cell survival following UV-irradiation were studied in each cell line.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA400021
Entities
People
- Isabel Mellon
Organizations
- University of Kentucky