Analysis of genetic interactions of DNA repair pathways

DNA修复途径的遗传相互作用分析

• 批准号: 13480228
• 负责人: TAKEDA Shunichi
• 金额: $ 9.66万
• 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-13480228/
• 关键词: DNA damage; DNA replication; Translesion DNA synthesis; Homologous DNA recombinatior; DNA polymerase; DT40; Sister chromatid exchange; 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，复制叉不可避免地会在受损的 DNA 处停滞。克服 DNA 损伤的能力是复制机制的一个基本特征。最近发现了多种特殊聚合酶，使细胞能够复制并克服各种形式的损伤。或者，同源重组可用于重新启动跨病变的 DNA 复制。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 对跨损伤合成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，我们旨在从其他模型系统的结果角度总结我们目前对 DT40 复制后修复的理解。

项目成果

A.Fujimori, S.Tachiiri, E.Sonoda, L.H.Thompson, P.K.Dhar, M.Hiraoka, S.Takeda, Y.Zhang, M.Reth, M.Takata: "Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells"EMBO J.. 20. 5513-5520 (2001)

A.Fujimori、S.Tachiiri、E.Sonoda、L.H.Thompson、P.K.Dhar、M.Hiraoka、S.Takeda、Y.Zhang、M.Reth、M.Takata：“Rad52 在维持染色体功能方面部分替代了 Rad51 旁系同源物 XRCC3

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

M.Takata, M.S.Sasaki, E.Sonoda, T.Fukushima, J.Albala, S.Swagemakers, R.Kanaar, L.H.Thompson, S.Takeda: "Targeted disruption of the RAD51B, a member of RAD51-related gene family, impairs homologous recombination and repair of crosslink DNA damages"Mol.Cel

M.Takata、M.S.Sasaki、E.Sonoda、T.Fukushima、J.Albala、S.Swagemakers、R.Kanaar、L.H.Thompson、S.Takeda：“有针对性地破坏 RAD51B（RAD51 相关基因家族的成员），

Yamashita, Y. M., Okada, T., Matsusaka, T, SonodaI, 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、SonodaI, E.、Cho, Z.、Araki, K.、Tateishi, S.、Yamaizumi, M. 和 Takeda, S：“RAD18 和 RAD54 共同致力于