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

Journal Article (Journal Article)

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 syndrome. In addition, simple repeats are unstable in certain forms of colorectal cancer, suggesting a defect in DNA replication or repair. 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 polymerases slipping during replication, and that some types of colorectal cancer may reflect mutations in genes involved in DNA mismatch repair.

Full Text

Duke Authors

Cited Authors

  • Strand, M; Prolla, TA; Liskay, RM; Petes, TD

Published Date

  • September 16, 1993

Published In

Volume / Issue

  • 365 / 6443

Start / End Page

  • 274 - 276

PubMed ID

  • 8371783

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/365274a0


  • eng

Conference Location

  • England