Mutations of two PMS homologues in hereditary nonpolyposis colon cancer

Nature. 1994 Sep 1;371(6492):75-80. doi: 10.1038/371075a0.


Hereditary nonpolyposis colorectal cancer (HNPCC) is one of man's commonest hereditary diseases. Several studies have implicated a defect in DNA mismatch repair in the pathogenesis of this disease. In particular, hMSH2 and hMLH1 homologues of the bacterial DNA mismatch repair genes mutS and mutL, respectively, were shown to be mutated in a subset of HNPCC cases. Here we report the nucleotide sequence, chromosome localization and mutational analysis of hPMS1 and hPMS2, two additional homologues of the prokaryotic mutL gene. Both hPMS1 and hPMS2 were found to be mutated in the germline of HNPCC patients. This doubles the number of genes implicated in HNPCC and may help explain the relatively high incidence of this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases*
  • Amino Acid Sequence
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA
  • DNA Repair Enzymes*
  • DNA-Binding Proteins*
  • Genes, Fungal
  • Humans
  • Mismatch Repair Endonuclease PMS2
  • Molecular Sequence Data
  • MutL Proteins
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Sequence Homology, Amino Acid
  • Sequence Tagged Sites
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Neoplasm Proteins
  • PMS1 protein, human
  • DNA
  • Adenosine Triphosphatases
  • PMS2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Proteins
  • DNA Repair Enzymes

Associated data

  • GENBANK/U13695
  • GENBANK/U13696