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Dissection of the ATPase switch controlling papillomavirus DNA replication initiation
Reference
C17187
Principal Investigator / Supervisor
Dr C Sanders
Co-Investigators /
Co-Supervisors
Institution
University of Sheffield
Department
Genomic Medicine
Funding type
Research
Value (£)
196,244
Status
Completed
Type
Research Grant
Start date
01/05/2002
End date
31/08/2005
Duration
40 months
Abstract
ATPase switches are often found at regulated steps in DNA replication initiation, but how they work is not understood. BPV-1 replication requires the initiator protein E1 and the transcription factor E2. E1 and E2 bind cooperatively to the viral origin (ori) to form a sequence specific to E1E2-ori complex. In a subsequent ATP-dependent step, E1E2-ori is converted to a multimeric E1-ori complex and E2 is displaced. Thus, ATP appears to drive E1-ori formation by coupling ATP hydrolysis to changes in protein-protein and protein-DNA interactions at ori. I propose to pinpoint the ATP dependent step by mutagenesis and dissect the switch mechanism using protein-DNA cross-linking techniques to fine-map protein-DNA interactions; kinetic assays to characterise the effects of ATP on protein-protein interactions, and proteases as probes for ATP-dependent structural changes in E1.
Summary
unavailable
Committee
Closed Committee - Biochemistry & Cell Biology (BCB)
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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