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Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair

Nature volume 365, pages 274–276 (1993)Cite this article

A Correction to this article was published on 07 April 1994

Abstract

THE genomes of all eukaryotes contain tracts of DNA in which a single base or a small number of bases is repeated. Expansions of such tracts have been associated with several human disorders including the fragile X syndrome1. In addition, simple repeats are unstable in certain forms of colorectal cancer, suggesting a defect in DNA replication or repair2—4. We show here that mutations in any three yeast genes involved in DNA mismatch repair (PMS1, MLH1 and MSH2) lead to 100- to 700-fold increases in tract instability, whereas mutations that eliminate the proof-reading function of DNA polymerases have little effect. The meiotic stability of the tracts is similar to the mitotic stability. These results suggest that tract instability is associated with DNA poly-merases slipping during replication, and that some types of colo-rectal cancer may reflect mutations in genes involved in DNA mismatch repair.

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Author notes

  1. Tomas A. Prolla & R. Michael Liskay

    Present address: Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, Oregon, 97201-3011, USA

Authors and Affiliations

  1. Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina, 27599-3280, USA

    Micheline Strand & Thomas D. Petes

  2. Department of Molecular Biophysics and Biochemistry and,

    Tomas A. Prolla

  3. Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, 06510-3219, USA

    R. Michael Liskay

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Strand, M., Prolla, T., Liskay, R. et al. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365, 274–276 (1993). https://doi.org/10.1038/365274a0

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