| Project/Area Number |
15390153
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Virology
|
|---|
| Research Institution | Aichi Cancer Center |
|---|
Principal Investigator |
TSURUMI Tatsuya Aichi Cancer Center, Division of Virology, Chief, 腫瘍ウイルス学部, 部長 (90172072)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
DAIKOKU Tohru Aichi Cancer Center, Division of Virology, Senior Researcher, 腫瘍ウイルス学部, 主任研究員 (80291409)
ISOMURA Hiroki Aichi Cancer Center, Division of Virology, Senior Researcher, 腫瘍ウイルス学部, 主任研究員 (20294415)
SHIRATA Noriko Aichi Cancer Center, Division of Virology, Research Resident, 腫瘍ウイルス学部, リサーチレジデント (90416165)
IWAHORI Satoko Aichi Cancer Center, Division of Virology, Research Resident, 腫瘍ウイルス学部, リサーチレジデント (80416164)
菅谷 豊 愛知県がんセンター(研究所), 腫瘍ウイルス学部, リサーチレジデント
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥5,500,000 (Direct Cost: ¥5,500,000)
|
|---|
| Keywords | Epstein-Barr virus / MCM / phosphorylation / protein kinase / chromosomal DNA replication / lytic infection / helicase / Epstein-Barr virus / ATM / DNA複製 / DNAチェックポイント / p53 / RB / EBV / 潜伏感染 / 溶解感染 / CDK阻害剤 |
|---|
| Research Abstract |
Induction of Epstein-Barr virus lytic replication from latent state blocks cell cycle progression and induces ATM DNA damage checkpoint signaling. Phosphorylated ATM and MRN complex are clustered to the sites of viral genome synthesis in nuclei. Here we report that the 32 kDa subunit of replication protein A (RPA) is extensively phosphorylated when lytic replication was induced. Although the total levels of the RPA proved constant throughout the lytic infection, the levels of DNA-bound form increased as lytic infection proceeded. The phosphorylated RPA was recruited and retained in viral replication compartments as well as phosphorylated ATM. The phosphorylation sites on RPA-32 were accorded with those by ATM and DNAPK that were activated during EBV lytic infection. Since hyper-phosphorylation of RPA32 in response to DNA damage causes a change in RPA conformation that down-regulates activity in DNA replication but participates in DNA repair process. Collectively, the EBV lytic program might actively inhibit chromosomal DNA replication through phosphorylation of RPA32 and allows hyperphosphorylated RPA to be involved in recombination and/or repair of viral DNA genome in the viral replication compartments.
|
