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Molecular and Cellular Biology, May 2003, p. 3152-3162, Vol. 23, No. 9
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.9.3152-3162.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Long CTG Tracts from the Myotonic Dystrophy Gene Induce Deletions and Rearrangements during Recombination at the APRT Locus in CHO Cells

James L. Meservy,1 R. Geoffrey Sargent,1 Ravi R. Iyer,2 Fung Chan,1 Gregory J. McKenzie,3 Robert D. Wells,2 and John H. Wilson1,3*

Verna and Marrs McLean Department of Biochemistry and Molecular Biology,1 Department of Molecular and Human Genetics, Baylor College of Medicine,3 Institute of Biosciences and Technology, Center for Genome Research, Texas A & M University, Houston, Texas 770302

Received 11 October 2002/ Returned for modification 26 November 2002/ Accepted 3 February 2003

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)17, (CTG)98, and (CTG)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)98 and (CTG)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)98 and (CTG)183 cells that were not recombinant at APRT. Instead, they displayed high frequencies of small changes in repeat number. The (CTG)17 repeats were stable in all assays. These studies indicate that homologous recombination strongly destabilizes long tracts of CTG repeats.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-5760. Fax: (713) 796-9438. E-mail: jwilson{at}bcm.tmc.edu.

Molecular and Cellular Biology, May 2003, p. 3152-3162, Vol. 23, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.9.3152-3162.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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