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Originally published In Press as doi:10.1074/jbc.M102670200 on June 26, 2001

J. Biol. Chem., Vol. 276, Issue 35, 33011-33018, August 31, 2001
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The Interaction of DNA Mismatch Repair Proteins with Human Exonuclease I*

Christoph SchmutteDagger , Margaret M. Sadoff, Kang-Sup Shim, Samir Acharya, and Richard Fishel§

From the Genetics and Molecular Biology Program, Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Exonucleolytic degradation of DNA is an essential part of many DNA metabolic processes including DNA mismatch repair (MMR) and recombination. Human exonuclease I (hExoI) is a member of a family of conserved 5' right-arrow 3' exonucleases, which are implicated in these processes by genetic studies. Here, we demonstrate that hExoI binds strongly to hMLH1, and we describe interaction regions between hExoI and the MMR proteins hMSH2, hMSH3, and hMLH1. In addition, hExoI forms an immunoprecipitable complex with hMLH1/hPMS2 in vivo. The study of interaction regions suggests a biochemical mechanism of the involvement of hExoI as a downstream effector in MMR and/or DNA recombination.

* This work was supported by National Institutes of Health Grant CA56542 (to R. F.).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.

Dagger To whom reprint requests may be addressed: Kimmel Cancer Center, BLSB933, Thomas Jefferson University, 233 S. 10th St., Philadelphia, PA 19107. Tel.: 213-503-1346; Fax: 215-923-1098; E-mail: cschmutte@lac.jci.tju.edu.

§ To whom reprint requests may be addressed: Kimmel Cancer Center, BLSB933, Thomas Jefferson University, 233 S. 10th St., Philadelphia, PA 19107. Tel.: 213-503-1346; Fax: 215-923-1098; E-mail: rfishel@hendrix.jci.tju.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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