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Probing DNA recognition and catalysis in a DNA glycosylase super-family

ReferenceB11484
Principal Investigator / Supervisor Dr Renos Savva
Co-Investigators /
Co-Supervisors
Professor Geoffrey Baldwin, Professor Laurence Pearl
Institution Birkbeck College
DepartmentBiological Sciences
Funding typeResearch
Value (£) 162,399
StatusCompleted
TypeResearch Grant
Start date 01/11/1999
End date 01/11/2002
Duration36 months

Abstract

There are two distinct classes of enzyme that are responsible for the removal of uracil from DNA; the uracil-DNA glycosylases (UDG) and the uracil/thymine:guanine mismatch-DNA glycosylases (MUG/TDG). Structural studies have revealed a remarkable similarity of form and function, despite clear biochemical differences, which may be explained by a number of key amino acid substitutions at the active sites of the enzymes. As a result, there exists two distinct mechanisms for the recognition and removal of the DNA lesion. We intend to elucidate these mechanisms by using a multidisciplinary approach to the study of UDG and MUG. This will involve mutagenesis to switch the active site residues of each enzyme and analysis of the mutants using single turnover kinetics alongside structural studies of the mutants, both alone and in enzyme-DNA complexes.

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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