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 Bioljournal_title
Molecular and cellular biologyauthors
Nicolaides NC,Littman SJ,Modrich P,Kinzler KW,Vogelstein Bdoi
10.1128/mcb.18.3.1635subject
Has Abstractpub_date
1998-03-01 00:00:00pages
1635-41issue
3eissn
0270-7306issn
1098-5549journal_volume
18pub_type
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pub_type: 杂志文章
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