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Cancer Lett. 2007 May 8;249(2):148-56. Epub 2006 Oct 9.

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

Author information

1
Department of Biology, Sacred Heart University, 5151 Park Ave., Fairfield, CT 06825, USA. descheness@sacredheart.edu

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.

PMID:
17029773
PMCID:
PMC2366906
DOI:
10.1016/j.canlet.2006.08.008
[Indexed for MEDLINE]
Free PMC Article

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