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Letters to Nature

Nature 368, 258-261 (17 March 1994) | doi:10.1038/368258a0; Accepted 28 February 1994

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

C. Eric Bronner*, Sean M. Baker*, Paul T. Morrison†, Gwynedd Warren‡, Leslie G. Smith*, Mary Kay Lescoe§, Michael Kaneparallel, Christine Earabino†, James Lipfordparallel, Annika Lindblom, Pia Tannergård, Roni J. Bollag‡#, Alan R. Godwin‡#, David C. Ward‡**, Magnus Nordenskj⊘ld, Richard Fishel§, Richard Kolodnerparallel† & R. Michael Liskay*††

  1. * Department of Molecular and Medical Genetics, L103, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97201-3098, USA
  2. † Molecular Biology Core Facility, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
  3. ‡ Department of Genetics
  4. **Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06510, USA
  5. § Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont 05405, USA
  6. parallel 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
  7. Department of Molecular Medicine, Karolinska Hospital, S-171 76 Stockholm, Sweden
  8. †† To whom correspondence should be addressed.
  9. # Present addresses: Institute for Molecular Medicine and Genetics, CB-2803 Sanders Research and Education Building Medical College of Georgia, Augusta, Georgia 30912, USA (R.J.B.); Department of Human Genetics, Bldg 533, Suite 5400, University of Utah, Salt Lake City, Utah 84112, USA (A.R.G.).
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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.