2002 Fiscal Year Final Research Report Summary
ROLES FOR VERTEBRATE ATM IN CELL CYCLE CHECKPOINT CONTROL
| Project/Area Number |
13680776
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | KANAZAWA UNIVERSITY |
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Principal Investigator |
YAMAMOTO Ken-ichi KANAZAWA UNIVERSITY, CANCER RESEARCH INSTITUTE, PROFESSOR, がん研究所, 教授 (60115285)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Hiroko KANAZAWA UNIVERSITY, CANCER RESEARCH INSTITUTE, ASSISTANT, がん研究所, 助手 (20126585)
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| Project Period (FY) |
2001 – 2002
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| Keywords | CELL CYCLE / GENE DISRUPTION / CHICKEN DT40 CELLS / DNA DAMAGE / ARG / RAD 51 / RAD 9 / RAD 17 |
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| Research Abstract |
c-Abl tyrosine kinase is activated by DNA damage in an ataxia telangiectasia mutated (ATM)-dependent manner, and plays important roles in growth arrest and apoptosis. Arg (abl-related gene) is an only known homologue of c-Abl, and shares considerable structural and sequence homology with c-Abl in the N-terminal SH3, SH2 and tyrosine kinase domains. However, Arg roles in cellular response to DNA damage are unknown. To study possible roles for Arg in cellular response to ionizing radiation (IR), we generated Arg-/- cells from a chicken B cell line (DT40) by targeted disruption. We found that, unlike c-Abl-/-DT40 cells (1) but similar to ATM-/-DT40 cells (2), ionizing radiation (IR)-induced Rad51 focus formation is reduced in Arg-/-DT40 cells. This is consistent with the findings that Arg-/-DT40 cells display hypersensitivity to IR, elevated frequencies of IR-induced chromosomal aberrations, and reduced targeted integration frequencies. All of these abnormalities in DNA damage repair are also observed in ATM-/- but not in c-Abl-/-DT40 cells (1, 2). Finally, we found that Arg interacts with and phosphorylates Rad51 in 293T cells. These results suggest that Arg plays a role in homologous recombinational DNA repair by phosphorylating Rad51.
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[Publications] Arimura, Y., Ogimoto, M., Mitomo, K., Katagiri, T., Yamamoto, K., Volarevjc, S., Mizuno, K., and Yakura, H.: "CD45 is required for CD40-induced inhibition of DNA synthesis and regulation of c-Jun NH2-terminal kinase and p38 in BAL-17 B cells"J. Biol. Chem.. 276. 8550-8556 (2001)
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[Publications] Xiang, S., Kumano, T., Iwasaki, I., Sun, X., Yoshioka, K., and Yamamoto, K.: "The J domain of Tpr2 regulates its interaction with the proapoptotic and cell cycle checkpoint protein, Rad9"Biochem. Biophys. Res. Comm.. 287. 932-940 (2001)
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[Publications] Muraoka, K., Shimizu, K., Sun, X., Tani, T., Izumi, R., Miwa, K., and Yamamoto, K.: "Flavonoids exert diverse inhibitory effects on the activation of NF-κB"Transpl. Proc.. 34. 1335-1340 (2002)
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[Publications] Li, Y., Shimizu, H., Xiang, S., Maru, Y., Takao, N., and Yamamoto, K.: "Arg tyrosine kinase is involved in homologous recombinational DNA repair"Biochem. Biophys. Res. Comm.. 299. 697-702 (2002)
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