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    Biochem Biophys Res Commun. 1996 Aug 5;225(1):289-95.

    A carboxy terminal domain of the hMSH-2 gene product is sufficient for binding specific mismatched oligonucleotides.

    Whitehouse A, Taylor GR, Deeble J, Phillips SE, Meredith DM, Markham AF.

    Molecular Medicine Unit, St. Jame's University Hospital, Leeds, United Kingdom. whitehouse@stjames.leeds.ac.uk

    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.

    PMID: 8769132 [PubMed - indexed for MEDLINE]

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