Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, 31027 Toulouse, France.
Int J Mol Sci. 2017 Dec 5;18(12):2611. doi: 10.3390/ijms18122611.
Within the nucleus, sub-nuclear domains define territories where specific functions occur. Nuclear bodies (NBs) are dynamic structures that concentrate nuclear factors and that can be observed microscopically. Recently, NBs containing the p53 binding protein 1 (53BP1), a key component of the DNA damage response, were defined. Interestingly, 53BP1 NBs are visualized during G1 phase, in daughter cells, while DNA damage was generated in mother cells and not properly processed. Unlike most NBs involved in transcriptional processes, replication has proven to be key for 53BP1 NBs, with replication stress leading to the formation of these large chromatin domains in daughter cells. In this review, we expose the composition and organization of 53BP1 NBs and focus on recent findings regarding their regulation and dynamics. We then concentrate on the importance of the replication stress, examine the relation of 53BP1 NBs with DNA damage and discuss their dysfunction.
在核内,亚核域定义了特定功能发生的区域。核体(NBs)是浓缩核因子的动态结构,可以在显微镜下观察到。最近,已经定义了含有 p53 结合蛋白 1(53BP1)的核体,53BP1 是 DNA 损伤反应的关键组成部分。有趣的是,在 G1 期,在子细胞中可以观察到 53BP1 NB,而在母细胞中产生的 DNA 损伤并未得到妥善处理。与大多数参与转录过程的 NB 不同,复制已被证明对 53BP1 NB 至关重要,复制应激导致这些大染色质域在子细胞中形成。在这篇综述中,我们揭示了 53BP1 NB 的组成和组织,并重点介绍了最近关于其调控和动态的发现。然后,我们集中讨论复制应激的重要性,研究 53BP1 NB 与 DNA 损伤的关系,并讨论它们的功能障碍。