A naturally occurring hPMS2 mutation can confer a dominant negative mutator phenotype.

Abstract:

:Defects in mismatch repair (MMR) genes result in a mutator phenotype by inducing microsatellite instability (MI), a characteristic of hereditary nonpolyposis colorectal cancers (HNPCC) and a subset of sporadic colon tumors. Present models describing the mechanism by which germ line mutations in MMR genes predispose kindreds to HNPCC suggest a "two-hit" inactivation of both alleles of a particular MMR gene. Here we present experimental evidence that a nonsense mutation at codon 134 of the hPMS2 gene is sufficient to reduce MMR and induce MI in cells containing a wild-type hPMS2 allele. These results have significant implications for understanding the relationship between mutagenesis and carcinogenesis and the ability to generate mammalian cells with mutator phenotypes.

journal_name

Mol Cell Biol

authors

Nicolaides NC,Littman SJ,Modrich P,Kinzler KW,Vogelstein B

doi

10.1128/mcb.18.3.1635

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

1635-41

issue

3

eissn

0270-7306

issn

1098-5549

journal_volume

18

pub_type

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