Abstract

EXCEED THE SPACE PROVIDED.
The aim of this research is to understand (i) the mechanism of initiation of herpes virus DNA replication, (ii) the mechanism of inversion that occurs during herpes virus DNA replication and (iii) the factors that influence the development of viral latency in herpes virus-infected neuronal cells. We anticipate that these studies will provide us with an insight into the replication, recombination and latency of a significant class of human pathogens. The investigation will be organized along the following lines. A. Analysis of the stimulation of binding of multimeric origin binding protein (UL9 protein) to Oris, an origin of HSV-1 DNA replication, by the cellular hTid-1 DnaJ chaperone. B. Role of neural F box protein (NFB42) in HSV- 1 latency. 1. Ubiquitination and degradation of UL9 protein upon binding NFB42. 2. Investigation of state of phosphorylation of UL9 protein on its interaction with NFB42. C. Role of endonuclease G in the initiation of sequence inversion in the HSV- 1 genome. 1. Studies of a sequence cleavage by endonuclease G. 2. Effect of HSV- 1 infection on levels of endonuclease G. 3. Cellular localization of endonuclease G pre- and post HSV-1 infection 4. Interaction of endonuclease G with other proteins. 5. Effect of suppression of endonuclease G on a-sequence-mediated recombination. PERFORMANCE SITE ========================================Section End===========================================

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI026538-18
Application #
6838773
Study Section
Biochemistry Study Section (BIO)
Program Officer
Beisel, Christopher E
Project Start
1988-07-01
Project End
2007-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
18
Fiscal Year
2005
Total Cost
$360,000
Indirect Cost

  Institution

Name
Stanford University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Huang, Ke-Jung; Ku, Chia-Chi; Lehman, I Robert (2006) Endonuclease G: a role for the enzyme in recombination and cellular proliferation. Proc Natl Acad Sci U S A 103:8995-9000
Eom, Chi-Yong; Heo, Won Do; Craske, Madeleine L et al. (2004) The neural F-box protein NFB42 mediates the nuclear export of the herpes simplex virus type 1 replication initiator protein (UL9 protein) after viral infection. Proc Natl Acad Sci U S A 101:4036-40
Eom, Chi-Yong; Lehman, I Robert (2003) Replication-initiator protein (UL9) of the herpes simplex virus 1 binds NFB42 and is degraded via the ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A 100:9803-7
Eom, Chi-Yong; Lehman, I Robert (2002) The human DnaJ protein, hTid-1, enhances binding of a multimer of the herpes simplex virus type 1 UL9 protein to oris, an origin of viral DNA replication. Proc Natl Acad Sci U S A 99:1894-8
He, X; Lehman, I R (2001) An initial ATP-independent step in the unwinding of a herpes simplex virus type I origin of replication by a complex of the viral origin-binding protein and single-strand DNA-binding protein. Proc Natl Acad Sci U S A 98:3024-8
He, X; Lehman, I R (2000) Unwinding of a herpes simplex virus type 1 origin of replication (Ori(S)) by a complex of the viral origin binding protein and the single-stranded DNA binding protein. J Virol 74:5726-8
Lee, S S; Lehman, I R (1999) The interaction of herpes simplex type 1 virus origin-binding protein (UL9 protein) with Box I, the high affinity element of the viral origin of DNA replication. J Biol Chem 274:18613-7
Lehman, I R; Boehmer, P E (1999) Replication of herpes simplex virus DNA. J Biol Chem 274:28059-62
Falkenberg, M; Elias, P; Lehman, I R (1998) The herpes simplex virus type 1 helicase-primase. Analysis of helicase activity. J Biol Chem 273:32154-7
Boehmer, P E; Lehman, I R (1997) Herpes simplex virus DNA replication. Annu Rev Biochem 66:347-84

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