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AN EXAMINATION OF BINDING DIFFERENCES AMONG MISMATCH REPAIR RECOGNITION PROTEINS WITH MISMATCH AND CISPLATIN DAMAGED DNA

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abstract
Mismatch repair is a major mechanism for the correction of replication errors in all organisms and increases the fidelity of DNA replication. Mismatch repair proteins have also demonstrated involvement in cellular response to the DNA damaging agent cisplatin. Cells deficient in mismatch repair have shown resistance to the cytotoxic effects of cisplatin treatment. Proposed mechanistic models for mismatch repair involvement require recognition of the damage site. To examine these models, E. coli MutS, S. cerevisae MSH2-MSH6, and MSH2-MSH3 were expressed to perform fluorescence anisotropy binding experiments and to crystallize the proteins in complex with cisplatin damaged DNA for comparison to mismatch DNA binding. All three mismatch repair (MMR) recognition complexes proved capable of binding cisplatin damaged DNA, but only MSH2-MSH6 demonstrated increased affinity towards cisplatin damage compared to undamaged DNA. Crystallization of a MMR protein with cisplatin damaged DNA was unsuccessful, but the methods presented here may be useful in further attempts.
subject
DNA repair
DNA damage
contributor
Rector, Brian (author)
Scarpinato, Karin (committee chair)
Hollis, Thomas (committee member)
Horita, David (committee member)
Lowther, W. Todd (committee member)
date
2010-05-07T18:48:04Z (accessioned)
2010-06-18T19:00:04Z (accessioned)
2010-05-07T18:48:04Z (available)
2010-06-18T19:00:04Z (available)
2010-05-07T18:48:04Z (issued)
degree
Biochemistry & Molecular Biology (discipline)
identifier
http://hdl.handle.net/10339/14920 (uri)
language
en_US (iso)
publisher
Wake Forest University
rights
Release the entire work immediately for access worldwide. (accessRights)
title
AN EXAMINATION OF BINDING DIFFERENCES AMONG MISMATCH REPAIR RECOGNITION PROTEINS WITH MISMATCH AND CISPLATIN DAMAGED DNA
type
Thesis

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