Mikolaskova B, Jurcik M, Cipakova I, Kretova M, Chovanec M, Cipak L
Department of Genetics, Biomedical Research Center, Cancer Research Institute, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovakia.
Curr Genet. 2018 Oct;64(5):971-983. doi: 10.1007/s00294-018-0819-7. Epub 2018 Mar 1.
Endogenous and exogenous factors can severely affect the integrity of genetic information by inducing DNA damage and impairing genome stability. The protection of genome integrity is ensured by the so-called "DNA damage response" (DDR), a set of evolutionary-conserved events that, triggered upon DNA damage detection, arrests the cell cycle, and attempts DNA repair. Here, we review the role of the DDR proteins as post-transcriptional regulators of gene expression, in addition to their roles in DNA damage recognition, signaling, and repair. At the same time, we discuss recent insights into how pre-mRNA splicing factors go beyond their splicing activities and play direct functions in detecting, signaling, and repairing DNA damage. The importance of extensive two-way crosstalk and interaction between the RNA processing and the DDR stems from growing evidence that the defects of their communication lead to genomic instability.
内源性和外源性因素可通过诱导DNA损伤和损害基因组稳定性，严重影响遗传信息的完整性。基因组完整性的保护由所谓的“DNA损伤反应”（DDR）来确保，这是一组进化保守的事件，在检测到DNA损伤时触发，使细胞周期停滞，并尝试进行DNA修复。在这里，我们除了回顾DDR蛋白在DNA损伤识别、信号传导和修复中的作用外，还将探讨其作为基因表达的转录后调节因子的作用。同时，我们讨论了最近关于前体mRNA剪接因子如何超越其剪接活性，并在检测、信号传导和修复DNA损伤中发挥直接作用的见解。RNA加工与DDR之间广泛的双向串扰和相互作用的重要性源于越来越多的证据表明，它们之间通讯的缺陷会导致基因组不稳定。
