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Role of divalent metal ions and conformational changes in the mechanism of a flap endonuclease

Reference	B19466
Principal Investigator / Supervisor	Professor Jon Sayers
Co-Investigators / Co-Supervisors	Professor Jane Grasby, Dr Ihtshamul Haq
Institution	University of Sheffield
Department	Genomic Medicine
Funding type	Research
Value (£)	195,348
Status	Completed
Type	Research Grant
Start date	01/11/2003
End date	30/09/2007
Duration	47 months

Abstract

Flap endonucleases are required for DNA replication and repair. They are extensively commercially exploited e.g. in genotyping assays. The mechanistic details of catalysis remain obscure. The enzyme contains two distinct divalent metal ion binding sites. We have demonstrated that only one metal site is essential for structure-specific cleavage, whereas both are required for exonuclease activity. To fully understand the enzymatic mechanism we will use a combination of kinetic and thermodynamic approaches. Specifically, quantitative enzymology, calorimetry and site-directed mutagenesis will be applied to unravel the mechanism of this intriguing enzyme. Such a multidisciplinary approach has yet to be applied to these important enzymes.

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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