Length of CTG·CAG repeats determines the influence of mismatch repair on genetic instability

Parniewski, Pawel, Jaworski, Adam, Wells, Robert D. and Bowater, Richard P. (2000) Length of CTG·CAG repeats determines the influence of mismatch repair on genetic instability. Journal of Molecular Biology, 299 (4). pp. 865-874. ISSN 0022-2836

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Abstract

We showed previously that mutations in methyl-directed mismatch repair of Escherichia coli reduced the occurrence of large deletions in (CTG·CAG)175 repeats contained on plasmids. By contrast, other workers reported that mutations in mismatch repair increase the frequency of small-length changes in the shorter (CTG·CAG)64. Using plasmids with a variety of lengths and purity of (CTG·CAG) repeats, we have resolved these apparently conflicting observations. We show that all lengths of (CTG·CAG) repeats are subject to small-length changes (<eight repeats) upon inactivation of the mismatch repair pathway. However, large deletions (>eight repeats) in (CTG·CAG)(n) occur more readily in cells with active mismatch repair. The frequency of large deletions is proportional to the tract length; in our assays they become prominent in tracts greater than 100 repeats. Interruptions in repeat purity enhance the occurrence of large deletions. In addition, we observed a high level of incidence of deletions in (CTG·CAG) repeats for cultures passing repeatedly through stationary phase during long-term growth experiments of all strains (i.e. with active or inactive mismatch repair). These results agree with current theories on mismatch repair acting on DNA slippage events that occur in DNA triplet-repeats. (C) 2000 Academic Press.

Item Type:	Article
Uncontrolled Keywords:	deletions,dna,genetic instability,mismatch repair,triplet-repeats,biophysics,structural biology,molecular biology ,/dk/atira/pure/subjectarea/asjc/1300/1304
Faculty \ School:	Faculty of Science > School of Biological Sciences
Related URLs:	https://www.scopus.com/pages/publication...
Depositing User:	LivePure Connector
Date Deposited:	28 May 2026 08:37
Last Modified:	28 May 2026 08:37
URI:	https://ueaeprints.uea.ac.uk/id/eprint/103179
DOI:	10.1006/jmbi.2000.3796

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