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Spontaneous mutations ataprt locus in a mammalian cell line defective in mismatch recognition

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Somatic Cell and Molecular Genetics

Abstract

Clone B is a CHO cell line that showns a moderate mutator phenotype as a consequence of a defect in mismatch recognition. To identify the classes of mutation that accumulate spontaneously in a functional gene, we isolated and sequenced 54 clone B spontaneous mutants at the adenine phosphoribosyltransferase gene. This spectrum was compared to 42 mutants collected in the parental cells. Rates of AT→TA transversions and frameshifts were strikingly increased in clone B (almost eight- and sixfold, respectively). Minor increases were also observed for GC→TA transversions and GC→AT transition rates. Frameshifts occurred in repeated sequences, and a large proportion were losses of 2 bases occurring in dinucleotide runs of a type similar to microsatellite sequences. AT→TA transversions clustered in regions of secondary structure and their formation might be explained by slippage-mediated mechanisms. These data indicate that an important function of mismatch recognition is in repair of extrahelical bases generated by misalignment during DNA replication.

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Authors and Affiliations

  1. Section of Chemical Carcinogenesis, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    Patricia Hess, Gabriele Aquilina, Eugenia Dogliotti & Margherita Bignami

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  1. Patricia Hess
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  2. Gabriele Aquilina
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  3. Eugenia Dogliotti
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  4. Margherita Bignami
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This work was partially supported by a grant from the CNR/ACRO.

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Hess, P., Aquilina, G., Dogliotti, E. et al. Spontaneous mutations ataprt locus in a mammalian cell line defective in mismatch recognition. Somat Cell Mol Genet 20, 409–421 (1994). https://doi.org/10.1007/BF02257458

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