Molecular Analysis of homologous recombination-mediated gene trageting

同源重组介导的基因定位的分子分析

• 批准号: 13557010
• 负责人: TAKEDA Shunichi
• 金额: $ 8.83万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557010/
• 关键词: DNA damage; DNA replication; Translesion DNA synthesis; Homologous DNA recombination; DNA polymerase; DT40; Sister chromatid exchange; 相同DM組換え; 相同DNA組み換え; DNA修復; チェックポイント; DT40細胞; 遺伝子治療

During each cell cycle replication forks inevitably stall at damaged DNA. The ability to overcome DNA lesions is an essential feature of the replication machinery. A large variety of specialized polymerases have recently been discovered that enable cells to replicate past various forms of damage. Alternatively homologous recombination can be used to restart DNA replication across the lesion. Genetic studies have shed light on the impact of these two post replication repair pathways in bacteria and yeast. In vertebrates, however, a genetic approach to study post replication repair has been compromised because most of the genes involved appear to be essential for embryonic development. We have taken advantage of the chicken cell line DT40 to perform a genetic analysis of translesion synthesis and homologous recombination and to characterize genetic interactions between these two pathways in vertebrates. In this article we aim to summarize our current understanding of post replication repair in DT40 in the perspective of results from other model systems.

在每个细胞周期中，复制分叉不可避免地在DNA受损时停止。克服DNA损伤的能力是复制机制的基本特征。最近发现了多种特殊的聚合酶，它们使细胞能够复制过去各种形式的损伤。或者同源重组可用于重新启动DNA复制横跨病变。遗传学研究揭示了细菌和酵母中这两种复制后修复途径的影响。然而，在脊椎动物中，研究复制后修复的遗传方法已经受到损害，因为大多数涉及的基因似乎对胚胎发育至关重要。我们利用鸡细胞系DT40进行了翻译合成和同源重组的遗传分析，并表征了这两种途径在脊椎动物中的遗传相互作用。在本文中，我们旨在从其他模型系统的结果的角度总结我们目前对DT40复制后修复的理解。

项目成果

M.Takata: "Conserved domains in the chicken homologue of BRCA2"Oncogene. (in press). (2001)

M.Takata：“BRCA2 鸡同源物中的保守结构域”癌基因。

T.Fukushima: "Genetic analysis of the DNA-dependent protein kinase reveals an inhibitory role of Ku in late S-G2 phase DNA double-strand break repair"J.of Biological Chemistry. Vol.276. 44413-44418 (2001)

T.Fukushima：“DNA 依赖性蛋白激酶的基因分析揭示了 Ku 在 S-G2 期 DNA 双链断裂修复晚期的抑制作用”J.of Biological Chemistry。

M.Takata: "Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs"Mol.Cell.Biol.. 21. 2858-2866 (2001)

M.Takata：“五个 Rad51 旁系同源基因敲除突变体中的染色体不稳定性和缺陷重组修复”Mol.Cell.Biol.. 21. 2858-2866 (2001)

Takata, M., Tachiiri, S., Fujimori, A., Thompson, L.H., Miki.Y., Hiraoka, M., Takeda, S., Yamazoe, M.: "Conserved domains in the chicken homologue of BRCA2"Oncogene. 21. 1130-1134 (2002)

Takata, M.、Tachiiri, S.、Fujimori, A.、Thompson, L.H.、Miki.Y.、Hiraoka, M.、Takeda, S.、Yamazoe, M.：“BRCA2 鸡同源物中的保守域”癌基因

Yamashita, Y. M., Okada, T., Matsusaka, T., Sonoda, E., Cho, Z., Araki, K., Tateishi, S., Yamaizumi, M., and Takeda, S.: "RAD18 and RAD54 cooperatively contribute to maintenance of genomic stability in vertebrate cells"EMBO J. 21. 5558-5566 (2002)

Yamashita, Y. M.、Okada, T.、Matsusaka, T.、Sonoda, E.、Cho, Z.、Araki, K.、Tateishi, S.、Yamaizumi, M. 和 Takeda, S.：“RAD18 和 RAD54 合作