Project/Area Number |
13670306
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Virology
|
Research Institution | Japanese Foundation for Cancer Research |
Principal Investigator |
HAYASHI Yasuyuki Cancer Institute, Dept. of Gene Associate Member Research, 癌研究所・遺伝子研究施設部, 研究員 (90198862)
|
Co-Investigator(Kenkyū-buntansha) |
KOIKE Katsuro Cancer Institute, Dept. of Gene Member & Chief Research, 癌研究所・遺伝子研究施設部, 部長 (30085625)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | Hepatitis B virus (HBV) / DNA Replication / Linear replicative DNA / Recombination of DNA / Direct repeat / Virus-cell junction / Integration of HBV DNA / 修復 / HBV DNA組込み |
Research Abstract |
In the replication cycle of hepadnavirus DNA, the double-stranded linear form of viral DNA is generated as a minor replicative intermediate, which is efficiently converted to covalently-closed circular (ccc) DNA by intra-molecular recombination. We previously found a specific binding site , which is close to the 51 end region of the negative viral strant (DR1), in one terminal region of the double-stranded linear replicative hepatitis B virus (HBV) DNA. However, it is not known whether this site is required for the intra-molecular recombination of HBV DNA. In this study, we established HBV-producing system, in which the cccDNA appeared to be generated from the transfected linear or the linear replicative DNA by non-homologous end-joining (NHEJ) , or NHEJ or homologous recombination between terminally repeated sequences, respectively. When the specific binding site in the terminal region of transfected linear viral DNA was mutated, the cccDNA was generated merely by NHEJ. Results suggest that, the specific binding site in the terminal region of linear replicative HBV DNA is required for the intra-molecular recombination between terminally repeated sequences. On the other hand, the cellular site of HBV DNA integration is random.
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