The goals of this study are to better understand the mechanism of retroviral DNA integration into the host genome and to evaluate its potential for the practical application in gene therapy.
The specific aims are 1) to determine the role of ASV integrase (IN) in the nuclear entry and DNA targeting of the ASV preintegration complex focussing on the nuclear localization signal (NLS) and its potential interacting cellular proteins; and 2) to determine if DNA integration can be targeted to specific sites in host cell chromatin using ASV IN fusion protein.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA071515-02
Application #
2458269
Study Section
Experimental Virology Study Section (EVR)
Project Start
1996-09-30
Project End
2001-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Institute for Cancer Research
Department
Type
DUNS #
872612445
City
Philadelphia
State
PA
Country
United States
Zip Code
19111
Balasubramanian, Sangeetha; Rajagopalan, Muthukumaran; Bojja, Ravi Shankar et al. (2017) The conformational feasibility for the formation of reaching dimer in ASV and HIV integrase: a molecular dynamics study. J Biomol Struct Dyn 35:3469-3485
Andrake, Mark D; Skalka, Anna Marie (2015) Retroviral Integrase: Then and Now. Annu Rev Virol 2:241-64
Peretz, Yuval; Wu, Hong; Patel, Shayan et al. (2015) Inhibitor of DNA Binding 4 (ID4) is highly expressed in human melanoma tissues and may function to restrict normal differentiation of melanoma cells. PLoS One 10:e0116839
Poleshko, Andrey; Kossenkov, Andrew V; Shalginskikh, Natalia et al. (2014) Human factors and pathways essential for mediating epigenetic gene silencing. Epigenetics 9:1280-9
Haugh, Kelsey A; Shalginskikh, Natalia; Nogusa, Shoko et al. (2014) The interferon-inducible antiviral protein Daxx is not essential for interferon-mediated protection against avian sarcoma virus. Virol J 11:100
Poleshko, Andrey; Katz, Richard A (2014) Specifying peripheral heterochromatin during nuclear lamina reassembly. Nucleus 5:32-9
Skala, Anna Marie (2014) Retroviral DNA Transposition: Themes and Variations. Microbiol Spectr 2:
Skalka, Anna Marie (2014) Retroviral DNA Transposition: Themes and Variations. Microbiol Spectr 2:MDNA300052014
Poleshko, Andrey; Mansfield, Katelyn M; Burlingame, Caroline C et al. (2013) The human protein PRR14 tethers heterochromatin to the nuclear lamina during interphase and mitotic exit. Cell Rep 5:292-301
Bojja, Ravi Shankar; Andrake, Mark D; Merkel, George et al. (2013) Architecture and assembly of HIV integrase multimers in the absence of DNA substrates. J Biol Chem 288:7373-86

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