The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression

Winfried Edelmann, Asad Umar, Kan Yang, Joerg Heyer, Melanie Kucherlapati, Marie Lia, Burkhard Kneitz, Elena Avdievich, Kunhua Fan, Edmund Wong, Gray Crouse, Thomas Kunkel, Martin Lipkin, Richard D. Kolodner, Raju Kucherlapati

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Abstract

Repair of mismatches in DNA in mammalian cells is mediated by a complex of proteins that are members of two highly conserved families of genes referred to as MutS and MutL homologues. Germline mutations in several members of these families, MSH2, MSH6, MLH1, and PMS2, but not MSH3, are responsible for hereditary non-polyposis colorectal cancer. To examine the role of MSH3, we generated a mouse with a null mutation in this gene. Cells from Msh3-/- mice are defective in repair of insertion/deletion mismatches but can repair base-base mismatches. Msh3-/- mice develop tumors at a late age. When the Msh3-/- and Msh6-/- mutations are combined, the tumor predisposition phenotype is indistinguishable from Msh2-/- or Mlh1-/- mice. These results suggest that MSH3 cooperates with MSH6 in tumor suppression.

Original languageEnglish (US)
Pages (from-to)803-807
Number of pages5
JournalCancer Research
Volume60
Issue number4
StatePublished - Feb 15 2000

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Edelmann, W., Umar, A., Yang, K., Heyer, J., Kucherlapati, M., Lia, M., Kneitz, B., Avdievich, E., Fan, K., Wong, E., Crouse, G., Kunkel, T., Lipkin, M., Kolodner, R. D., & Kucherlapati, R. (2000). The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression. Cancer Research, 60(4), 803-807.