Positioning and functional structure of repliction time zones at the cystic fibrosis gene locus

囊性纤维化基因座复制时区的定位和功能结构

• 批准号: 5108898
• 负责人: Dr. Daniele Zink
• 金额: --
• 依托单位: Fach Anthropologie und Humangenetik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 1998
• 资助国家: 德国
• 起止时间: 1997-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5108898?language=en
• 关键词: Positioning; functional; structure; repliction; time

During the first two funding periods we investigated the dynamics of DNA replication. We could show, that large-scale movements are not involved in DNA replication 1,2. Therefore, we concentrated on the analysis of local replication dynamics. In results show that, in contrast to favored models 3-6, DNA as well as functional complexes of replication proteins display local dynamics. The protein complexes display local re-localizations, which are not due to movements of whole complexes, but due to local processes of assembly and disassembly of replication proteins. While the DNA poised to replicate can be translocated into these complexes, nascent DNA is extruded in an aggregated form into adjacent regions. Furthermore, the results showed that 93% of DNA aggregates, which replicated at a defined time point during S-phase, stably maintained their replication timing. These results strongly support the hypothesis, that chromosomes are organized into stable DNA aggregates (subchromosomal foci), which display a defined replication timing during S-phase 7-13. In order to further proof this hypothesis we will investigate the distinct replication time zones at the cystic fibrosis gene locus 14 during the next funding period. We will analyze, whether these distinct time zones are organized into stable subchromosomal foci displaying a defined regulation with regard to replication, transcription, and nuclear positioning.

在前两个资助期，我们研究了DNA复制的动态。我们可以证明，大规模的运动不参与DNA复制1，2。因此，我们集中分析了局部复制的动力学。结果表明，与受欢迎的模型3-6相比，DNA以及复制蛋白的功能复合体表现出局部动力学。蛋白质复合体表现出局部重新定位，这不是由于整个复合体的移动，而是由于复制蛋白质的局部组装和拆解过程。当准备复制的DNA可以转移到这些复合体中时，新生的DNA以聚集的形式挤出到相邻的区域。此外，结果表明，在S期特定时间点复制的DNA聚集体中，93%的DNA聚集体稳定地保持了其复制时间。这些结果有力地支持了这样的假设，即染色体被组织成稳定的DNA聚集体(亚染色体焦点)，在S阶段7-13期间表现出明确的复制时间。为了进一步证明这一假设，我们将在下一个资金阶段调查囊性纤维化基因第14位的不同复制时区。我们将分析，这些不同的时区是否被组织成稳定的亚染色体焦点，显示出关于复制、转录和核定位的明确规则。