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DNA repair by O6-alkylguanine-DNA alkyltransferases
Reference
B14708
Principal Investigator / Supervisor
Dr David Mark Williams
Co-Investigators /
Co-Supervisors
Institution
University of Sheffield
Department
Chemistry
Funding type
Research
Value (£)
125,500
Status
Completed
Type
Research Grant
Start date
08/05/2001
End date
07/07/2003
Duration
26 months
Abstract
O6-Alkylguanine-DNA alkytransferases (ATases) repair O6-alkyguanine lesions in DNA by transferring the alkyl group to an active site cysteine via an irreversible, stoichiometric reaction. The human protein (hAT) is also an important therapeutic target in chemotherapy treatment. Crystal structures of the E. coli (C-Ada) and human (hAT) proteins have suggested a base flipping mechanism, akin to other DNA processing enzymes, but how this might occur is still not fully understood. We aim to study the repair reaction using oligonucleotide substrates containing nucleoside analogues capable of mechanism-based cross-linking to the protein for crystallography and ones containing fluorophores for stopped flow analysis using fluorescence.
Summary
unavailable
Committee
Closed Committee - Biomolecular Sciences (BMS)
Research Topics
X – not assigned to a current Research Topic
Research Priority
X – Research Priority information not available
Research Initiative
X - not in an Initiative
Funding Scheme
X – not Funded via a specific Funding Scheme
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