Cell Biology and Epigenetics, Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany.
Nucleus. 2020 Dec;11(1):66-82. doi: 10.1080/19491034.2020.1744415.
Decades of investigation on genomic DNA have brought us deeper insights into its organization within the nucleus and its metabolic mechanisms. This was fueled by the parallel development of experimental techniques and has stimulated model building to simulate genome conformation in agreement with the experimental data. Here, we will discuss our recent discoveries on the chromatin units of DNA replication and DNA damage response. We will highlight their remarkable structural similarities and how both revealed themselves as clusters of nanofocal structures each on the hundred thousand base pair size range corresponding well with chromatin loop sizes. We propose that the function of these two global genomic processes is determined by the loop level organization of chromatin structure with structure dictating function. 3D-SIM: 3D-structured illumination microscopy; 3C: chromosome conformation capture; DDR: DNA damage response; FISH: fluorescent in situ hybridization; Hi-C: high conformation capture; HiP-HoP: highly predictive heteromorphic polymer model; IOD: inter-origin distance; LAD: lamina associated domain; STED: stimulated emission depletion microscopy; STORM: stochastic optical reconstruction microscopy; SBS: strings and binders switch model; TAD: topologically associated domain.
几十年来对基因组 DNA 的研究使我们更深入地了解了其在核内的组织及其代谢机制。这得益于实验技术的平行发展，并刺激了模型构建，以模拟与实验数据一致的基因组构象。在这里，我们将讨论我们最近在 DNA 复制和 DNA 损伤反应的染色质单位方面的发现。我们将强调它们显著的结构相似性，以及这两者如何各自揭示出纳米焦点结构簇，每个簇的大小都在十万碱基对范围内，与染色质环大小很好地对应。我们提出，这两个全球基因组过程的功能是由染色质结构的环级组织决定的，结构决定功能。3D-SIM：3D 结构照明显微镜；3C：染色体构象捕获；DDR：DNA 损伤反应；FISH：荧光原位杂交；Hi-C：高构象捕获；HiP-HoP：高度预测的异质聚合物模型；IOD：起始原点距离；LAD：层粘连蛋白相关域；STED：受激发射耗尽显微镜；STORM：随机光学重建显微镜；SBS：字符串和结合物开关模型；TAD：拓扑相关域。
