Abstract
The human MSH-2 gene product is a member of a highly conserved family of proteins which are involved in post-replication mismatch repair. hMSH-2 is homologous to Escherichia coli (E. coli) MutS and Sacchromyces cerevisiae MSH-1 and MSH-2 proteins, which recognise heteroduplex DNA at the sites of all single base mismatches and deletions or insertions up to 4 base pairs. hMSH-2 is one of the hereditary non-polyposis colorectal cancer (HNPCC) tumor suppressor genes, and maps to human chromosome 2p16. Alterations in the coding region of the hMSH-2 gene result in a mutator phenotype with marked instability of microsatellite sequences, indicative of a deficiency in DNA repair. It has been shown that purified hMSH-2 binds specifically to nucleotide mismatches in double-stranded DNA. Here we demonstrate that a region of high homology between the members of this class of proteins contains a type A nucleotide binding site consensus sequence which has ATPase activity and is sufficient to bind DNA containing specific mismatched residues.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenosine Triphosphatases / metabolism
-
Amino Acid Sequence
-
Bacterial Proteins / metabolism
-
Base Sequence
-
Binding Sites
-
Cloning, Molecular
-
Conserved Sequence
-
DNA / chemistry
-
DNA / metabolism*
-
DNA Primers
-
DNA Repair
-
DNA-Binding Proteins / metabolism
-
Escherichia coli / metabolism
-
Escherichia coli Proteins*
-
Fungal Proteins / metabolism
-
Humans
-
Mitochondrial Proteins
-
Molecular Sequence Data
-
MutS DNA Mismatch-Binding Protein
-
MutS Homolog 2 Protein
-
Oligodeoxyribonucleotides / chemistry
-
Oligodeoxyribonucleotides / metabolism*
-
Oligopeptides
-
Peptides / chemistry
-
Peptides / metabolism
-
Polymerase Chain Reaction
-
Proto-Oncogene Proteins / biosynthesis
-
Proto-Oncogene Proteins / chemistry
-
Proto-Oncogene Proteins / metabolism*
-
Recombinant Fusion Proteins / isolation & purification
-
Recombinant Fusion Proteins / metabolism
-
Saccharomyces cerevisiae / metabolism
-
Saccharomyces cerevisiae Proteins*
-
Sequence Homology, Amino Acid
Substances
-
Bacterial Proteins
-
DNA Primers
-
DNA-Binding Proteins
-
Escherichia coli Proteins
-
Fungal Proteins
-
MSH1 protein, S cerevisiae
-
Mitochondrial Proteins
-
Oligodeoxyribonucleotides
-
Oligopeptides
-
Peptides
-
Proto-Oncogene Proteins
-
Recombinant Fusion Proteins
-
Saccharomyces cerevisiae Proteins
-
DNA
-
FLAG peptide
-
Adenosine Triphosphatases
-
MSH2 protein, S cerevisiae
-
MSH2 protein, human
-
MutS DNA Mismatch-Binding Protein
-
MutS Homolog 2 Protein
-
MutS protein, E coli