The E705K mutation in hPMS2 exerts recessive, not dominant, effects on mismatch repair

Suzanne M. Deschênes, Guy Tomer, Megan Nguyen, Naz Erdeniz, Nicole C. Juba, Natalia Sepúlveda, Jenna E. Pisani, R. Michael Liskay

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The hPMS2 mutation E705K is associated with Turcot syndrome. To elucidate the pathogenesis of hPMS2-E705K, we modeled this mutation in yeast and characterized its expression and effects on mutation avoidance in mammalian cells. We found that while hPMS2-E705K (pms1-E738K in yeast) did not significantly affect hPMS2 (Pms1p in yeast) stability or interaction with MLH1, it could not complement the mutator phenotype in MMR-deficient mouse or yeast cells. Furthermore, hPMS2-E705K/pms1-E738K inhibited MMR in wild-type (WT) mammalian cell extracts or yeast cells only when present in excess amounts relative to WT PMS2. Our results strongly suggest that hPMS2-E705K is a recessive loss-of-function allele.

Original languageEnglish (US)
Pages (from-to)148-156
Number of pages9
JournalCancer Letters
Volume249
Issue number2
DOIs
StatePublished - May 8 2007

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Keywords

  • Mismatch repair
  • PMS2
  • Turcot syndrome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Deschênes, S. M., Tomer, G., Nguyen, M., Erdeniz, N., Juba, N. C., Sepúlveda, N., Pisani, J. E., & Michael Liskay, R. (2007). The E705K mutation in hPMS2 exerts recessive, not dominant, effects on mismatch repair. Cancer Letters, 249(2), 148-156. https://doi.org/10.1016/j.canlet.2006.08.008