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.

在每个细胞周期的复制叉期间，不可避免地会停滞在受损的DNA上。克服DNA病变的能力是复制机制的重要特征。最近发现了各种各样的专业聚合酶，使细胞能够复制各种形式的损害。或者，可以使用同源重组来重新启动整个病变的DNA复制。遗传研究揭示了这两个复制后修复途径在细菌和酵母中的影响。然而，在脊椎动物中，复制修复后进行研究的遗传方法已受到损害，因为所涉及的大多数基因似乎对于胚胎发育至关重要。我们利用了鸡细胞系DT40来对跨性别和同源重组进行遗传分析，并表征脊椎动物中这两种途径之间的遗传相互作用。在本文中，我们旨在总结我们当前对DT40中复制后修复的理解，从其他模型系统的结果角度来看。

项目成果

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)

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。

Sale, J.E.: "Ablation of XRCC2/3 transforms immunoglobulin V gene conversion into somatic hypermutation"Nature. 412:9. (2001)

Sale, J.E.：“XRCC2/3 的消融将免疫球蛋白 V 基因转化为体细胞超突变”《自然》杂志。

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