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Mutation in the DNA mismatch repair gene homologue hMLH 1 is associated with hereditary non-polyposis colon cancer

Nature volume 368, pages 258–261 (1994)Cite this article

Abstract

THE human DNA mismatch repair gene homologue, hMSH2, on chromosome 2p is involved in hereditary non-polyposis colon cancer (HNPCC)1,2. On the basis of linkage data, a second HNPCC locus was assigned to chromosome 3p21-23 (ref. 3). Here we report that a human gene encoding a protein, hMLHl (human MutL homologue), homologous to the bacterial DNA mismatch repair protein MutL, is located on human chromosome 3p21.3-23. We propose that hMLHl is the HNPCC gene located on 3p because of the similarity of the hMLHl gene product to the yeast DNA mismatch repair protein, MLH14,5, the coincident location of the hMLHl gene and the HNPCC locus on chromosome 3, and hMLHl missense mutations in affected individuals from a chromosome 3-linked HNPCC family.

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Author notes

  1. Roni J. Bollag

    Present address: Institute for Molecular Medicine and Genetics, CB-2803 Sanders Research and Education Building Medical College of Georgia, Augusta, Georgia, 30912, USA

  2. Alan R. Godwin

    Present address: Department of Human Genetics, University of Utah, Bldg 533, Suite 5400, Salt Lake City, Utah, 84112, USA

Authors and Affiliations

  1. Department of Molecular and Medical Genetics, L103, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon, 97201-3098, USA

    C. Eric Bronner, Sean M. Baker, Leslie G. Smith & R. Michael Liskay

  2. Molecular Biology Core Facility, Dana Farber Cancer Institute, Boston, Massachusetts, 02115, USA

    Paul T. Morrison, Christine Earabino & Richard Kolodner

  3. Department of Genetics,

    Gwynedd Warren, Roni J. Bollag, Alan R. Godwin & David C. Ward

  4. Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    David C. Ward

  5. Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont, 05405, USA

    Mary Kay Lescoe & Richard Fishel

  6. Division of Cellular and Molecular Biology, Dana Farber Cancer institute, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Michael Kane, James Lipford & Richard Kolodner

  7. Department of Molecular Medicine, Karolinska Hospital, S-171 76, Stockholm, Sweden

    Annika Lindblom, Pia Tannergård & Magnus Nordenskj⊘ld

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  1. C. Eric Bronner
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  16. Richard Fishel
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Bronner, C., Baker, S., Morrison, P. et al. Mutation in the DNA mismatch repair gene homologue hMLH 1 is associated with hereditary non-polyposis colon cancer. Nature 368, 258–261 (1994). https://doi.org/10.1038/368258a0

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