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DNA repair by O6-alkylguanine-DNA alkyltransferases

ReferenceB14708
Principal Investigator / Supervisor Dr David Mark Williams
Co-Investigators /
Co-Supervisors
Institution University of Sheffield
DepartmentChemistry
Funding typeResearch
Value (£) 125,500
StatusCompleted
TypeResearch Grant
Start date 08/05/2001
End date 07/07/2003
Duration26 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 TopicsX – not assigned to a current Research Topic
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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