Functional analysis of genes involved in maintenance of chromosome stability and homologous recombination

参与维持染色体稳定性和同源重组的基因的功能分析

基本信息

批准号：
12213059
负责人：
TAKATA Minoru
金额：
$ 28.16万
依托单位：
Kawasaki Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12213059/
关键词：
homologous recombination DNA repair DT 40 cells Rad51 paralogs Fanconi anemia sister chromatid exchanges 姉妹染色分体交換相同組替えジーンターゲティング複製後修復相同組み換え Rad51 Rad51ファミリー Rad52 XRCC3

项目摘要

DNA repair mediated by homologous recombination (HR) is an important mechanism in promoting genome stability and preventing carcinogenesis. In this project, we disrupted putative HR regulators including five Rad51 paralogs and Fanconi anemia genes in chicken cell line DT40.(1) Cells lacking each of Rad51 paralogs all displayed very similar HR defects such as cisplatin sensitivity, increased chromosomal aberrations, and loss of Rad51 focus formation or gene targeting efficiencies. Since Rad51 paralogs interact with each other, these results suggest that Rad51 paralogs work together as a functional unit in mediating HR reactions through Rad51.(2) We found that Rad52 (an HR factor) and Xrcc3 (one of Rad51 paralogs) exhibited synthetic lethality in DT40 cells, indicating that there are some overlapping functions between these two molecules.(3) DT40 mutants lacking FA genes displayed HR defects such as decreased gene targeting efficiencies, a decreased gene conversion frequency at immunoglobulin locus, and impaired HR repair of restriction enzyme-induced chromosonal double strand breaks. These results were the first formal demonstration of the role of FA genes in HR.(4) We showed epistasis between BLM helicase and the FA pathway in terms of SCE frequency and sensitivities to MMC or cisplatin. BLM helicase seems to be one of the effector molecules of the FA pathway.

同源重组（HR）介导的DNA修复是促进基因组稳定性和预防致癌作用的重要机制。 In this project, we disrupted putative HR regulators including five Rad51 paralogs and Fanconi anemia genes in chicken cell line DT40.(1) Cells lacking each of Rad51 paralogs all displayed very similar HR defects such as cisplatin sensitivity, increased chromosomal aberrations, and loss of Rad51 focus formation or gene targeting efficiencies.由于RAD51旁系同源物相互作用，因此这些结果表明Rad51旁系同源物在介导HR反应的功能单元中一起工作。缺乏FA基因表现出人力资源缺陷，例如靶向效率的降低，免疫球蛋白基因座的基因转化频率降低以及限制性酶诱导的染色体染色体双绞线的HR修复受损。这些结果是FA基因在人力资源中的作用的第一个正式证明。（4）我们在SCE频率和对MMC或顺铂的敏感性方面表明了BLM解旋酶与FA途径之间的上毒。 BLM解旋酶似乎是FA途径的效应分子之一。

项目成果

期刊论文数量（78）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Takata M et al.: "Conserved domains in the chicken homologue of BRCA2"Oncogene. 21・7. 1130-1134 (2002)

Takata M 等人：“BRCA2 鸡同源物中的保守结构域”Oncogene 21・7 1130-1134 (2002)。

DOI：
发表时间：
期刊：
影响因子：
0
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通讯作者：

Takata, M. et al.: "Conserved domains in the chicken homologue of BRCA2"Oncogene. 21(7). 1130-1134 (2002)

Takata, M. 等人：“BRCA2 鸡同源物中的保守结构域”癌基因。

DOI：
发表时间：
期刊：
影响因子：
0
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(2004)-DNA crosslink repair protein SNM1A interacts with PIAS1 in nuclear focus formation.

(2004)-DNA 交联修复蛋白 SNM1A 在核焦点形成中与 PIAS1 相互作用。

DOI：
发表时间：
2004
期刊：
Mol Cell Biol. 24(24)
影响因子：
0
作者：
Hirano S.et al.;Yamamoto K.et al.;Yamamoto K. et al.;Hatanaka A.et al.;Hirano S.et al.;Yamamoto K.et al.;M Ishiai.et al.;Hirano S. et al.;M.Ishiai et al.
通讯作者：
M.Ishiai et al.

Tauchi, H. et al.: "Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells"Nature. 420(6911). 93-98 (2002)

Tauchi, H. 等人：“Nbs1 对于高等脊椎动物细胞中通过同源重组进行 DNA 修复至关重要”。