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ToolsJaworski, Adam, Rosche, William A., Gellibolian, Robert, Kang, Seongman, Shimizu, Miho, Bowater, Richard P., Sinden, Richard R. and Wells, Robert D. (1995) Mismatch repair in Escherichia coli enhances instability of (CTG)n triplet repeats from human hereditary diseases. Proceedings of the National Academy of Sciences of the United States of America, 92 (24). pp. 11019-11023. ISSN 0027-8424
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Abstract
Long CTG triplet repeats which are associated with several human hereditary neuromuscular disease genes are stabilized in ColE1-derived plasmids in Escherichia coli containing mutations in the methyl-directed mismatch repair genes (mutS, mutL, or mutH). When plasmids containing (CTG)180 were grown for about 100 generations in mutS, mutL, or mutH strains, 60-85% of the plasmids contained a full-length repeat, whereas in the parent strain only about 20% of the plasmids contained the full-length repeat. The deletions occur only in the (CTG)180 insert, not in DNA flanking the repeat. While many products of the deletions are heterogeneous in length, preferential deletion products of about 140, 100, 60, and 20 repeats were observed. We propose that the E. coli mismatch repair proteins recognize three-base loops formed during replication and then generate long single-stranded gaps where stable hairpin structures may form which can be bypassed by DNA polymerase during the resynthesis of duplex DNA. Similar studies were conducted with plasmids containing CGG repeats; no stabilization of these triplets was found in the mismatch repair mutants. Since prokaryotic and human mismatch repair proteins are similar, and since several carcinoma cell lines which are defective in mismatch repair show instability of simple DNA microsatellites, these mechanistic investigations in a bacterial cell may provide insights into the molecular basis for some human genetic diseases.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | general,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1000 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Biosciences Teaching and Education Research Faculty of Science > Research Groups > Molecular Microbiology Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 27 May 2026 11:06 |
| Last Modified: | 27 May 2026 11:06 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/103170 |
| DOI: | issn:0027-8424 |
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