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 journalArticle

114 Citations (Scopus)

Abstract

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
Volume6
Issue number2
DOIs
StatePublished - Aug 2004

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DNA Mismatch Repair
Missense Mutation
DNA Repair
Neoplasms
Hereditary Nonpolyposis Colorectal Neoplasms
Genomic Instability
Mutation Rate
DNA Damage
Carcinogenesis
Yeasts
Mutation
DNA
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility. / Yang, Guohze; Scherer, Stefan J.; Shell, Scarlet S.; Yang, Kan; Kim, Mimi; Lipkin, Martin; Kucherlapati, Raju; Kolodner, Richard D.; Edelmann, Winfried.

In: Cancer Cell, Vol. 6, No. 2, 08.2004, p. 139-150.

Research output: Contribution to journalArticle

Yang, G, Scherer, SJ, Shell, SS, Yang, K, Kim, M, Lipkin, M, Kucherlapati, R, Kolodner, RD & Edelmann, W 2004, 'Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility', Cancer Cell, vol. 6, no. 2, pp. 139-150. https://doi.org/10.1016/j.ccr.2004.06.024
Yang, Guohze ; Scherer, Stefan J. ; Shell, Scarlet S. ; Yang, Kan ; Kim, Mimi ; Lipkin, Martin ; Kucherlapati, Raju ; Kolodner, Richard D. ; Edelmann, Winfried. / Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility. In: Cancer Cell. 2004 ; Vol. 6, No. 2. pp. 139-150.
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