Navigation auf zora.uzh.ch

Search ZORA

ZORA (Zurich Open Repository and Archive)

Identification of hMutLbeta, a heterodimer of hMLH1 and hPMS1

Räschle, M; Marra, Giancarlo; Nyström-Lahti, M; Schär, P; Jiricny, J (1999). Identification of hMutLbeta, a heterodimer of hMLH1 and hPMS1. Journal of Biological Chemistry, 274(45):32368-32375.

Abstract

hMLH1 and hPMS2 function in postreplicative mismatch repair in the form of a heterodimer referred to as hMutLalpha. Tumors or cell lines lacking this factor display mutator phenotypes and microsatellite instability, and mutations in the hMLH1 and hPMS2 genes predispose to hereditary non-polyposis colon cancer. A third MutL homologue, hPMS1, has also been reported to be mutated in one cancer-prone kindred, but the protein encoded by this locus has so far remained without function. We now show that hPMS1 is expressed in human cells and that it interacts with hMLH1 with high affinity to form the heterodimer hMutLbeta. Recombinant hMutLalpha and hMutLbeta, expressed in the baculovirus system, were tested for their activity in an in vitro mismatch repair assay. While hMutLalpha could fully complement extracts of mismatch repair-deficient cell lines lacking hMLH1 or hPMS2, hMutLbeta failed to do so with any of the different substrates tested in this assay. The involvement of the latter factor in postreplicative mismatch repair thus remains to be demonstrated.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Biochemistry
Life Sciences > Molecular Biology
Life Sciences > Cell Biology
Language:English
Date:1999
Deposited On:09 Jul 2010 08:27
Last Modified:04 Nov 2024 02:38
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1074/jbc.274.45.32368
PubMed ID:10542278

Metadata Export

Statistics

Citations

Dimensions.ai Metrics
152 citations in Web of Science®
152 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 09 Jul 2010
0 downloads since 12 months

Authors, Affiliations, Collaborations

Similar Publications