Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer

Nature. 1994 Mar 17;368(6468):258-61. doi: 10.1038/368258a0.


The human DNA mismatch repair gene homologue hMSH2, on chromosome 2p is involved in hereditary non-polyposis colon cancer (HNPCC). 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, hMLH1 (human MutL homologue), homologous to the bacterial DNA mismatch repair protein MutL, is located on human chromosome 3p21.3-23. We propose that hMLH1 is the HNPCC gene located on 3p because of the similarity of the hMLH1 gene product to the yeast DNA mismatch repair protein, MLH1, the coincident location of the hMLH1 gene and the HNPCC locus on chromosome 3, and hMLH1 missense mutations in affected individuals from a chromosome 3-linked HNPCC family.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carrier Proteins
  • Cells, Cultured
  • Chromosome Mapping
  • Chromosomes, Human, Pair 3
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Repair / genetics*
  • DNA, Neoplasm
  • Humans
  • Hybrid Cells
  • Molecular Sequence Data
  • MutL Protein Homolog 1
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Rodentia
  • Saccharomyces / genetics
  • Sequence Homology, Amino Acid


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA, Neoplasm
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • MutL Protein Homolog 1

Associated data

  • GENBANK/U07343