Journal of Biological Chemistry
Volume 274, Issue 45, 5 November 1999, Pages 32368-32375
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ENZYMOLOGY
Identification of hMutLβ, a Heterodimer of hMLH1 and hPMS1*

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hMLH1 and hPMS2 function in postreplicative mismatch repair in the form of a heterodimer referred to as hMutLα. Tumors or cell lines lacking this factor display mutator phenotypes and microsatellite instability, and mutations in the hMLH1 andhPMS2 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 hMutLβ. Recombinant hMutLα and hMutLβ, expressed in the baculovirus system, were tested for their activity in an in vitro mismatch repair assay. While hMutLα could fully complement extracts of mismatch repair-deficient cell lines lacking hMLH1 or hPMS2, hMutLβ 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.

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This work was supported by grants from the Swiss National Science Foundation and the Sigfried-Juselius Fund.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.