Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility

Guohze Yang, Stefan J. Scherer, Scarlet S. Shell, Kan Yang, Mimi Kim, Martin Lipkin, Raju Kucherlapati, Richard D. Kolodner, Winfried Edelmann

Research output: Contribution to journalArticlepeer-review

133 Scopus citations


Mutations in DNA mismatch repair (MMR) genes cause hereditary nonpolyposis colorectal cancer (HNPCC), and MMR defects are associated with a significant proportion of sporadic cancers. MMR maintains genome stability and suppresses tumor formation by preventing the accumulation of mutations and by mediating an apoptotic response to DNA damage. We describe the analysis of a dominant MSH6 missense mutation in yeast and mice that causes loss of DNA repair function while having no effect on the apoptotic response to DNA damaging agents. Our results demonstrate that MSH6 missense mutations can effectively separate the two functions, and that increased mutation rates associated with the loss of DNA repair are sufficient to drive tumorigenesis in MMR-defective tumors.

Original languageEnglish (US)
Pages (from-to)139-150
Number of pages12
JournalCancer Cell
Issue number2
StatePublished - Aug 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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