
Mismatch repair, genetic stability and tumour avoidance.
Escherichia coli methyl-directed mismatch repair eliminates premutagenic lesions that arise via DNA biosynthetic errors; components of the repair system also block ectopic recombination between diverged DNA sequences. A mismatch-dependent, methyl-directed excision reaction that accounts for function of the system in replication fidelity has been reconstituted in a purified system dependent on ten activities. The reaction displays a broad specificity for mismatched base pairs and is characterized by an unusual bidirectional excision capability. Human cell nuclear extracts support strand-specific mismatch correction in a reaction that is similar to bacterial repair, with respect to both mismatch specificity and unusual features of mechanism. Like the bacterial system, the human pathway also functions in mutation avoidance because several classes of mutator human cells are deficient in the reaction. These include an alkylation-tolerance cell line that is resistant to the cytotoxic action of N-methyl-N'-nitro-nitrosoguanidine, as well as hypermutable RER+ tumour cells such as those associated with hereditary non-polyposis colon cancer. In vitro experiments indicate that the human repair reaction is dependent on at least six activities, excluding DNA ligase, and that distinct defects in the system can lead to the RER+ phenotype.
Duke Scholars
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- Phenotype
- Neoplasms
- Mutation
- Humans
- Evolutionary Biology
- DNA, Neoplasm
- DNA Repair
- 32 Biomedical and clinical sciences
- 31 Biological sciences
- 11 Medical and Health Sciences
Citation

Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Phenotype
- Neoplasms
- Mutation
- Humans
- Evolutionary Biology
- DNA, Neoplasm
- DNA Repair
- 32 Biomedical and clinical sciences
- 31 Biological sciences
- 11 Medical and Health Sciences