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

Micheline Strand, Tomas A. Prolla, R. Michael Liskay, Thomas D. Petes

Research output: Contribution to journalArticle

881 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)274-276
Number of pages3
JournalNature
Volume365
Issue number6443
DOIs
StatePublished - Jan 1 1993

ASJC Scopus subject areas

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