High-resolution analysis of the spatio-temporal control of the DNA replication activation

DNA 复制激活的时空控制的高分辨率分析

• 批准号: 232488461
• 负责人: Professorin Dr. Maria Cristina Cardoso
• 金额: --
• 依托单位: Arbeitsgruppe Cell Biology and Epigenetics
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/232488461?language=en
• 关键词: resolution; analysis; spatio; temporal; control

The mammalian cell has the challenge to duplicate its entire genome once and only once every time it divides. Our objective is to understand this central cell biological process at the level of the single replication unit and at the level of the whole genome. The basic mechanisms of DNA replication have been established by a powerful combination of genetics and in vitro biochemistry. From this body of work, it is clear that the fundamental features and components of DNA replication are well conserved throughout evolution from bacteria up to mammals. A comprehensive list of proteins that are involved in the process and their activities has been compiled, and it is now possible to provide a relatively detailed description of the DNA replication machinery on a molecular level. However, genomic DNA in eukaryotic cells is hierarchically packed within the nucleus and genome duplication requires the concerted effort of many thousands of individual replication units over time. As such, it is important to understand how DNA replication is regulated in space and time across the entire genome and within the cellular context.The goal of our project is to elucidate the spatio-temporal control of the activation mechanism of DNA replication in mammalian cells. In particular, we will address whether i) DNA higher order structure, ii) DNA modifications and iii) DNA (com)position in the nucleus regulate DNA replication dynamics. The outcome of our project should contribute to, on the one hand, the elucidation of the structure-functional dynamics of the DNA replication process in the cellular context and, on the other hand, provide evidence for its activation mechanism.

哺乳动物细胞面临的挑战是复制其整个基因组一次，而且每次分裂时只复制一次。我们的目标是在单个复制单位水平和整个基因组水平上了解这一中央细胞生物学过程。DNA复制的基本机制是通过遗传学和体外生物化学的强大结合而建立起来的。从这一系列工作中，很明显，DNA复制的基本特征和组成部分在从细菌到哺乳动物的整个进化过程中都得到了很好的保守。参与这一过程的蛋白质及其活动的全面清单已经汇编，现在可以在分子水平上提供对DNA复制机制的相对详细的描述。然而，真核细胞中的基因组DNA是按层次排列在细胞核内的，随着时间的推移，基因组复制需要数千个单独复制单位的协同努力。因此，了解DNA复制是如何在整个基因组和细胞环境中在空间和时间上被调控的是很重要的。我们的项目的目标是阐明哺乳动物细胞中DNA复制激活机制的时空控制。特别是，我们将讨论i)DNA高阶结构，ii)DNA修饰和iii)DNA(Com)在核中的位置是否调节DNA复制动力学。我们项目的成果一方面有助于阐明细胞内DNA复制过程的结构-功能动力学，另一方面为其激活机制提供证据。