A carboxy terminal domain of the hMSH-2 gene product is sufficient for binding specific mismatched oligonucleotides.
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.
Whitehouse
A
A
Molecular Medicine Unit, St. Jame's University Hospital, Leeds, United Kingdom. whitehouse@stjames.leeds.ac.uk
Taylor
G R
GR
Deeble
J
J
Phillips
S E
SE
Meredith
D M
DM
Markham
A F
AF
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D051719:MutS DNA Mismatch-Binding Protein; D051718:MutS Homolog 2 Protein; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; C078660:MSH1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D010455:Peptides; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; C085706:FLAG peptide; D000251:Adenosine Triphosphatases; C489751:MSH2 protein, S cerevisiae; C497172:MSH2 protein, human; D051719:MutS DNA Mismatch-Binding Protein; D051718:MutS Homolog 2 Protein; C497175:MutS protein, E coli