| Autor: |
Meservy, James L., Sargent, R. Geoffrey, Iyer, Ravi R., Fung Chan, McKenzie, Gregory J., Wells, Robert D., Wilson, John H. |
| Předmět: |
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| Zdroj: |
Molecular & Cellular Biology; May2003, Vol. 23 Issue 9, p3152, 11p, 2 Black and White Photographs, 5 Diagrams, 4 Charts |
| Abstrakt: |
Expansion of CTG triplet repeats in the 3' untranslated region of the DMPK gene causes the autosomal dominant disorder myotonic dystrophy. Instability of CTG repeats is thought to arise from their capacity to form hairpin DNA structures. How these structures interact with various aspects of DNA metabolism has been studied intensely for Escherichia coli and Saccharomyces cerevisiae but is relatively uncharacterized in mammalian cells. To examine the stability of (CTG)[sub 17], (CTG)[sub 98], and (CTG)[sub 183] repeats during homologous recombination, we placed them in the second intron of one copy of a tandemly duplicated pair of APRT genes. Cells selected for homologous recombination between the two copies of the APRT gene displayed distinctive patterns of change. Among recombinants from cells with (CTG)[sub 98] and (CTG)[sub 183], 5% had lost large numbers of repeats and 10% had suffered rearrangements, a frequency more than 50-fold above normal levels. Analysis of individual rearrangements confirmed the involvement of the CTG repeats. Similar changes were not observed in proliferating (CTG)[sub 98] and (CTG)[sub 183] cells that were not recombinant at APRT. Instead, they displayed high frequencies of small changes in repeat number. The (CTG)[sub 17] repeats were stable in all assays. These studies indicate that homologous recombination strongly destabilizes long tracts of CTG repeats. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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