2000 Fiscal Year Final Research Report Summary
Analysis of homologous DNA recombination using the chicken B-lymphocyte line
| Project/Area Number |
10044274
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TAKEDA Shunichi Kyoto Univ. Graduate school of Med. (Professor), 医学研究科, 教授 (60188191)
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| Co-Investigator(Kenkyū-buntansha) |
TAKATA Minoru kawasaki medical scool. immunology (Professor), 医学研究科, 教授 (30281728)
IWAI Yuko Kyoto Univ. Devision of integrated Life sciencc (Research assistant), 生命科学研究科, 助手 (10281726)
SONODA Eiichiro Kyoto Univ. Graduate school of Med. (Assistant Professor), 医学研究科, 助手 (50281093)
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| Project Period (FY) |
1998 – 2000
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| Keywords | DT40 / fumorigenesis / DNA repair / checkpoint / chemothrapy of cancer / homologous DNA recombination / ionizing radiation |
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| Research Abstract |
The department now has a solid base of very active research in the field of cellular response to DNA damage, including DNA repair, DNA Recombination, apoptosis, and cell cycle regulation.
(1) We have successfully generated DT40 mutants deficient in each of all the RAD52 epistasis group genes, and have found they are indeed involved in HR including gene targeting.
(2) We found that depletion of either Rad51 or Mrell causes chromosomal breaks like wild-type DT40 cells irradiated with X-rays. Since HR is involved with dsb repair, these observations suggest that dsbs occur frequently during the cell cycle in vertebrate cells and that HR is responsible for repairing such DNA damage.
(3) We reported significantly low levels of SCEs in all HR-deficient cell lines. This was an important finding as it established a direct correlation between HR-mediated repair and SCEs for the first time.
(4) Two major repair pathways exist in eukaryotes to tackle DNA dsbs : Non-homologous end-joining (NHEJ) and HR.We showed that homologous DNA recombiantion can mediate interactions between sister chromatids but not homologous chromosomes for DNA double-strand break repair in vertebrate cells.
Our scudies are relevant to analysis of oncogenesis caused by genetic instability, cancer therapy, and development of methods for gene therapy.
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[Publications] Y.Yamaguchi-Iwai, E.Sonoda, M.S.Sasaki, C.Morrison, T.Haraguchi, Y.Hiraoka, Y.M.Yamashita, T.Yagi, M.Takata, C.Price, N.Kakazu, and S.Takeda.: "Mrell is essential for the maintenance of chromosomal DNA in vertebrate cells."EMBO J.. 18. 6619-6629 (1999)
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