In this revised new application from a young independent investigator, a series of biophysical studies are proposed to investigate the mechanisms underlying the hypothesized coordinate regulation of papillomaviral transcription and papillomaviral DNA replication. The PI, Dr. Alexander, hypothesizes that this coordinate regulation is a consequence of competition between cellular transcription and replication factors and the viral E1 and E2 protein that regulate and contribute to transcription and replication.
The aims of this proposal are to evaluate the influence of these factors on each other's DNA binding, protein binding and enzymatic activities. The data gained from this study will be used to create a dynamic model of HPV transcription and replication control that will be broadly applicable to transcription and replication control in DNA viruses.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA081214-03
Application #
6513536
Study Section
Virology Study Section (VR)
Program Officer
Wong, May
Project Start
2000-07-01
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2004-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$207,900
Indirect Cost
Name
Duke University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Hall, Allison H S; Wan, Jing; Spesock, April et al. (2006) High potency silencing by single-stranded boranophosphate siRNA. Nucleic Acids Res 34:2773-81
Hall, Allison H S; Wan, Jing; Shaughnessy, Erin E et al. (2004) RNA interference using boranophosphate siRNAs: structure-activity relationships. Nucleic Acids Res 32:5991-6000
Deng, Su-Jun; Pearce, Kenneth H; Dixon, Eric P et al. (2004) Identification of peptides that inhibit the DNA binding, trans-activator, and DNA replication functions of the human papillomavirus type 11 E2 protein. J Virol 78:2637-41
Hall, Allison H S; Alexander, Kenneth A (2003) RNA interference of human papillomavirus type 18 E6 and E7 induces senescence in HeLa cells. J Virol 77:6066-9
Hartley, Kelly A; Alexander, Kenneth A (2002) Human TATA binding protein inhibits human papillomavirus type 11 DNA replication by antagonizing E1-E2 protein complex formation on the viral origin of replication. J Virol 76:5014-23