O6-Alkylguanine adducts : detection and biological significance
O6-Alkylguanine adducts : detection and biological significance
O6-alkylguanine DNA adducts represent significant intermediates in alkylating agent-induced carcinogenesis. A class-specific monoclonal antibody, recognising a range of O6-alkylguanines, has been isolated. Immobilisation of this antibody on a solid support has allowed its use in the immunoaffinity chromatography enrichment of O6-alkyl-2'-deoxyguanosine samples contaminated with normal nucleosides. The efficiency of this enrichment process has been determined by HPLC. The immunoaffinity column is capable of extracting picomolar amounts of adduct from a 107 excess of normal nucleosides.
Mismatch repair has been implicated in the cytotoxic effects of O6-alkylguanine adducts. MutS, the mismatch recognition enzyme in the E. coli mismatch repair pathway, has been shown to bind to oligonucleotide heteroduplex substrates containing O6-methyl, ethyl or n-butylguanine base-paired to either cytosine or thymidine. In each case, MutS exhibits a greater affinity for the heteroduplex where the O6-alkylguanine is base-paired to thymidine rather than cytosine.
University of Southampton
1998
Allinson, Sarah Louise
(1998)
O6-Alkylguanine adducts : detection and biological significance.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
O6-alkylguanine DNA adducts represent significant intermediates in alkylating agent-induced carcinogenesis. A class-specific monoclonal antibody, recognising a range of O6-alkylguanines, has been isolated. Immobilisation of this antibody on a solid support has allowed its use in the immunoaffinity chromatography enrichment of O6-alkyl-2'-deoxyguanosine samples contaminated with normal nucleosides. The efficiency of this enrichment process has been determined by HPLC. The immunoaffinity column is capable of extracting picomolar amounts of adduct from a 107 excess of normal nucleosides.
Mismatch repair has been implicated in the cytotoxic effects of O6-alkylguanine adducts. MutS, the mismatch recognition enzyme in the E. coli mismatch repair pathway, has been shown to bind to oligonucleotide heteroduplex substrates containing O6-methyl, ethyl or n-butylguanine base-paired to either cytosine or thymidine. In each case, MutS exhibits a greater affinity for the heteroduplex where the O6-alkylguanine is base-paired to thymidine rather than cytosine.
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Published date: 1998
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Local EPrints ID: 463437
URI: http://eprints.soton.ac.uk/id/eprint/463437
PURE UUID: a465b482-3023-4209-9603-7fa1e0be2b67
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Date deposited: 04 Jul 2022 20:51
Last modified: 04 Jul 2022 20:51
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Author:
Sarah Louise Allinson
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