Roles of DNA repair pathways in Sleeping Beauty transposition in vertebrate cells

DNA修复途径在脊椎动物细胞睡美人转座中的作用

• 批准号: 5429053
• 负责人: Professor Dr. Zoltan Ivics
• 金额: --
• 依托单位: Abteilung Medizinische Biotechnologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5429053?language=en
• 关键词: Roles; DNA; repair; pathways; Sleeping

Several factors determine which DNA repair pathways are used to heal the damage caused by movement of a transposable element, including the transposon itself, the structure of the lesion, the host organism, the status of the cell cycle, and whether transposition occurs in the soma or in the germline. The contribution of DNA repair to DNA transposition in vertebrate cells has not been previously addressed, due to the lack of active transposons in these species. Our research laboratory is using the Sleeping Beauty (SB) transposable element as a tool to probe transposon-host cell interactions in vertebrates. Our previous work has established that nonhomologous end joining and homologous recombination both contribute to the repair of SB-induced double-strand DNA breaks in mammalian somatic cells. The proposed project is aimed at surveying different cellular factors involved in DNA replication, repair and damage signaling for their potential roles in SB transposition. We propose to study the contribution of these factors in establishing a successful transposition event, and differential regulation of these processes through the cell cycle. Transposition-inflicted DNA damage differs form radiation-, retroviral integration-, restriction enzyme-, and V(D)J recombination-generated lesions. The proposed research might therefore provide important clues about differential regulation of transposition and other DNA recombination mechanisms, and extend our understanding of the principal molecular processes involved in cellular responses to DNA damage in mammalian cells.

有几个因素决定了哪些DNA修复途径被用于修复转座因子移动引起的损伤，包括转座子本身、损伤的结构、宿主生物体、细胞周期的状态以及转座是发生在索马还是发生在种系中。DNA修复对脊椎动物细胞中的DNA转座的贡献以前没有得到解决，因为这些物种中缺乏活性转座子。我们的研究实验室正在使用睡美人（SB）转座因子作为一种工具来探测脊椎动物中的转座子-宿主细胞相互作用。我们以前的工作已经确定，非同源末端连接和同源重组都有助于SB诱导的哺乳动物体细胞双链DNA断裂的修复。该项目旨在调查参与DNA复制，修复和损伤信号传导的不同细胞因子在SB转座中的潜在作用。我们建议研究这些因素在建立一个成功的转座事件的贡献，并通过细胞周期这些过程的差异调节。转座引起的DNA损伤不同于辐射、逆转录病毒整合、限制性内切酶和V（D）J重组产生的损伤。因此，拟议中的研究可能会提供重要的线索，转座和其他DNA重组机制的差异调节，并扩展我们对哺乳动物细胞中DNA损伤的细胞反应所涉及的主要分子过程的理解。