Base excision repair of U:G mismatches at a mutational hotspot in the p53 gene is more efficient than base excision repair of T:G mismatches in extracts of human colon tumors
- Resource Type
- Authors
- C, Schmutte; A S, Yang; R W, Beart; P A, Jones
- Source
- Cancer research. 55(17)
- Subject
- Endodeoxyribonucleases
Guanine
Base Sequence
DNA Repair
Molecular Sequence Data
Genes, p53
DNA Glycosylases
Deoxyribonuclease (Pyrimidine Dimer)
Colonic Neoplasms
Humans
Point Mutation
Uracil
Uracil-DNA Glycosidase
N-Glycosyl Hydrolases
Thymine
HeLa Cells
- Language
- ISSN
- 0008-5472
Approximately 50% of mutations that inactivate the p53 tumor suppressor gene in the germline and in colon tumors are C to T transitions at methylation sites (CpG sites). These mutations are believed to be caused by an endogenous mechanism and spontaneous deamination of 5-methyl-cytosine to T is likely to contribute significantly to this high mutation rate. The resulting T:G mismatches created by this process have been hypothesized to be less efficiently repaired than U:G mismatches formed by deamination of C. We have, therefore, performed the first study to directly compare rates of T:G versus U:G base excision repair at identical sites observed to be mutated in the p53 gene using extracts of human normal colon mucosa and colon carcinoma tissue. Mismatched U was excised up to 6000-fold more efficiently than T, suggesting that differences in repair efficiencies are the major source of C to T transition mutations at CpG sites in human tissues. The data also suggests that T:G mismatches are repaired by additional mechanisms in human cells.