Analysis of homologous DNA recombination using the chicken B-lymphocyte line

使用鸡 B 淋巴细胞系进行同源 DNA 重组分析

• 批准号: 10044274
• 负责人: TAKEDA Shunichi
• 金额: $ 4.42万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10044274/
• 关键词: DT40; fumorigenesis; DNA repair; checkpoint; chemothrapy of cancer; homologous DNA recombination; ionizing radiation; DNA相同組換え; Rad51; ジーンターゲティング; ヌクレオチド除去修復; 標的組み換え; ターゲットインテグレーション; 遺伝子ノックアウト; 電離放射線; Ku

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.

该部门现在在细胞对DNA损伤的响应领域中具有非常积极的研究基础，包括DNA修复，DNA重组，凋亡和细胞周期调节。（1）我们已经成功地产生了所有RAD52 Epistasis基因中缺乏DT40突变体的DT40突变体，并且确实发现了它们参与HR的CAR5或MR MR MR，我们发现了Deple。染色体断裂，例如用X射线照射的野生型DT40细胞。由于HR与DSB修复有关，因此这些观察结果表明DSB经常发生在脊椎动物细胞中的细胞周期期间，并且HR负责修复此类DNA损伤。（3）我们报告了所有HR缺乏的细胞系中SCE的水平显着较低。 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脊椎动物细胞。您的流行与分析遗传不稳定性，癌症治疗以及基因治疗方法的发展有关。

项目成果

M.Takata.M.S.Sasakl.S.Tachiiri.T.Fukushima.E.Sonoda.D.Schild.L.H.Thompson.and S.Takeda: "Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs."〔論文リスト:1〕Mol.Cell.Biol. (2001)

M. Takata。列表：1]Mol.Cell.Biol。

C.,Morrison,E.Sonoda,N.Takao,A.Shinohara,K.Yamamoto and S.Takeda: "Time controlling role of ATM in homologous recombinational repair of DNA damage."EMBO J. 19. 463-471 (2000)

C.,Morrison,E.Sonoda,N.Takao,A.Shinohara,K.Yamamoto 和 S.Takeda：“ATM 在 DNA 损伤同源重组修复中的时间控制作用。”EMBO J. 19. 463-471 (2000

Morrison C.,Shinohara A.,Sonoda E.,Yamaguchi-Iwai Y.,Takata M.,Weichselbaum RR.: "The Essential functions of human Rad51 are independent of ATP hydrolysis"Mol Cell Bio. 19. 6891-6897 (1999)

Morrison C.、Shinohara A.、Sonoda E.、Yamaguchi-Iwai Y.、Takata M.、Weichselbaum RR.：“人类 Rad51 的基本功能独立于 ATP 水解”Mol Cell Bio。

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)

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 和 S.Takeda：

M.Tanabe et al.: "Disruption of the HSF3 gene results in the severe reduction of heat shock gene expression and loss of thermotolerance." EMBO J.vol.17. 1750-1758 (1998)

M.Tanabe 等人：“HSF3 基因的破坏会导致热休克基因表达的严重减少和耐热性的丧失。”