PMID- 9488480
OWN - NLM
STAT- MEDLINE
DCOM- 19980319
LR  - 20240213
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 18
IP  - 3
DP  - 1998 Mar
TI  - A naturally occurring hPMS2 mutation can confer a dominant negative mutator 
      phenotype.
PG  - 1635-41
AB  - 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.
FAU - Nicolaides, N C
AU  - Nicolaides NC
AD  - Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA. 
      nnicolaides.@magainin.com
FAU - Littman, S J
AU  - Littman SJ
FAU - Modrich, P
AU  - Modrich P
FAU - Kinzler, K W
AU  - Kinzler KW
FAU - Vogelstein, B
AU  - Vogelstein B
LA  - eng
GR  - P50 CA062924/CA/NCI NIH HHS/United States
GR  - CA62924/CA/NCI NIH HHS/United States
GR  - CA71544/CA/NCI NIH HHS/United States
GR  - CA35494/CA/NCI NIH HHS/United States
GR  - R01 GM045190/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Bacterial Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (MSH3 protein, human)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (MutL protein, E coli)
RN  - 0 (MutS Homolog 3 Protein)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nucleic Acid Heteroduplexes)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.1.- (PMS2 protein, human)
RN  - EC 3.6.1.3 (Mismatch Repair Endonuclease PMS2)
RN  - EC 3.6.1.3 (MutL Proteins)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - *Adenosine Triphosphatases
MH  - Animals
MH  - Bacterial Proteins/metabolism
MH  - Cell Line
MH  - Cricetinae
MH  - *DNA Repair
MH  - *DNA Repair Enzymes
MH  - DNA-Binding Proteins/metabolism
MH  - *Escherichia coli Proteins
MH  - HeLa Cells
MH  - Humans
MH  - Mesocricetus
MH  - Mismatch Repair Endonuclease PMS2
MH  - *Multidrug Resistance-Associated Proteins
MH  - MutL Proteins
MH  - MutS Homolog 3 Protein
MH  - *Mutation
MH  - Neoplasm Proteins/biosynthesis/*genetics/metabolism
MH  - Nucleic Acid Heteroduplexes
MH  - Phenotype
PMC - PMC108878
EDAT- 1998/03/06 00:00
MHDA- 1998/03/06 00:01
PMCR- 1998/03/01
CRDT- 1998/03/06 00:00
PHST- 1998/03/06 00:00 [pubmed]
PHST- 1998/03/06 00:01 [medline]
PHST- 1998/03/06 00:00 [entrez]
PHST- 1998/03/01 00:00 [pmc-release]
AID - 1144 [pii]
AID - 10.1128/MCB.18.3.1635 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1998 Mar;18(3):1635-41. doi: 10.1128/MCB.18.3.1635.