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

Micheline Strand, Tomas A. Prolla, Robert (Mike) Liskay, Thomas D. Petes

Research output: Contribution to journalArticle

869 Citations (Scopus)

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 polyrnerases 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 polymerases slipping during replication, and that some types of colorectal cancer may reflect mutations in genes involved in DNA mismatch repair.

Original languageEnglish (US)
Pages (from-to)274-276
Number of pages3
JournalNature
Volume365
Issue number6443
StatePublished - Sep 16 1993

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DNA Mismatch Repair
Yeasts
Mutation
Colorectal Neoplasms
DNA
DNA-Directed DNA Polymerase
Eukaryota
DNA Replication
Genes
Reading
Genome

ASJC Scopus subject areas

  • General

Cite this

Strand, M., Prolla, T. A., Liskay, R. M., & Petes, T. D. (1993). Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature, 365(6443), 274-276.

Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. / Strand, Micheline; Prolla, Tomas A.; Liskay, Robert (Mike); Petes, Thomas D.

In: Nature, Vol. 365, No. 6443, 16.09.1993, p. 274-276.

Research output: Contribution to journalArticle

Strand, M, Prolla, TA, Liskay, RM & Petes, TD 1993, 'Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair', Nature, vol. 365, no. 6443, pp. 274-276.
Strand M, Prolla TA, Liskay RM, Petes TD. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature. 1993 Sep 16;365(6443):274-276.
Strand, Micheline ; Prolla, Tomas A. ; Liskay, Robert (Mike) ; Petes, Thomas D. / Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. In: Nature. 1993 ; Vol. 365, No. 6443. pp. 274-276.
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