Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, NY.
Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, NY
J Cell Biol. 2019 Aug 5;218(8):2444-2455. doi: 10.1083/jcb.201904202. Epub 2019 Jul 19.
Eukaryotic nuclei are organized into nuclear domains that unite loci sharing a common function. These domains are essential for diverse processes including (1) the formation of topologically associated domains (TADs) that coordinate replication and transcription, (2) the formation of specialized transcription and splicing factories, and (3) the clustering of DNA double-strand breaks (DSBs), which concentrates damaged DNA for repair. The generation of nuclear domains requires forces that are beginning to be identified. In the case of DNA DSBs, DNA movement and clustering are driven by actin filament nucleators. Furthermore, RNAs and low-complexity protein domains such as RNA-binding proteins also accumulate around sites of transcription and repair. The link between liquid-liquid phase separation and actin nucleation in the formation of nuclear domains is still unknown. This review discusses DSB repair domain formation as a model for functional nuclear domains in other genomic contexts.
真核细胞核组织成核域，将具有共同功能的基因座联合在一起。这些域对于多种过程是必不可少的，包括（1）形成拓扑关联域（TADs），以协调复制和转录，（2）形成专门的转录和剪接工厂，以及（3）DNA 双链断裂（DSBs）的聚类，将受损的 DNA 集中起来进行修复。核域的产生需要开始确定的力。就 DNA DSB 而言，DNA 的运动和聚类是由肌动蛋白丝引发剂驱动的。此外，RNA 和低复杂度蛋白结构域，如 RNA 结合蛋白，也在转录和修复部位周围积累。在核域形成过程中，液-液相分离和肌动蛋白引发之间的联系仍然未知。这篇综述讨论了 DSB 修复域的形成，作为其他基因组环境中功能性核域的模型。
