Journal Article

Relative Stabilities of Dinucleotide and Tetranucleotide Repeats in Cultured Mammalian Cells

Jung Sup Lee, Marsha G. Hanford, Jennifer L. Genova and RosannA. Farber

in Human Molecular Genetics

Volume 8, issue 13, pages 2567-2572
Published in print December 1999 | ISSN: 0964-6906
Published online December 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.13.2567
Relative Stabilities of Dinucleotide and Tetranucleotide Repeats in Cultured Mammalian Cells

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The differences in rates of frameshift mutations between a dinucleotide repeat sequence [(CA)17]and a tetranucleotide repeat sequence [(GAAA)17] have been determined in immortalized, non-tumorigenic, mis-match repair-proficient mouse cells and in mismatch repair-defective human colorectal cancer cells. Clones with mutations were selected on the basis of restoration of activity of a bacterial neomycin resistance gene whose reading frame was disrupted by insertion of the microsatellite upstream of the translation initiation codon. This gene was introduced into the cells on a plasmid, which integrated into the genome of the host cells. Mutation rates of the tetra-nucleotide repeat were much lower than those of the dinucleotide repeat in both cell types. In addition, independent subclones of the colorectal cancer cell line were assayed by PCR for instability of endogenous tetranucleotide and dinucleotide repeat sequences. In all cases, the mutation frequencies of the dinucleotide repeats were higher than those of the tetranucleotide repeats.

Journal Article.  3876 words.  Illustrated.

Subjects: Genetics and Genomics

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