Institute of Chemical Biology and Fundamental Medicine, SB RAS, 630090 Novosibirsk, Russia.
Laboratoire Structure-Activité des Biomolécules Normales et Pathologiques, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.
Int J Mol Sci. 2020 Sep 24;21(19):7020. doi: 10.3390/ijms21197020.
The fused in sarcoma (FUS) protein combines prion-like properties with a multifunctional DNA/RNA-binding domain and has functions spanning the regulation of RNA metabolism, including transcription, pre-mRNA splicing, mRNA transport and translation. In addition to its roles in RNA metabolism, FUS is implicated in the maintenance of DNA integrity. In this review, we examine the participation of FUS in major DNA repair pathways, focusing on DNA repair associated with poly(ADP-ribosyl)ation events and on how the interaction of FUS with poly(ADP-ribose) may orchestrate transient compartmentalisation of DNA strand breaks. Unravelling how prion-like RNA-binding proteins control DNA repair pathways will deepen our understanding of the pathogenesis of some neurological diseases and cancer as well as provide the basis for the development of relevant innovative therapeutic technologies. This knowledge may also extend the range of applications of poly(ADP-ribose) polymerase inhibitors to the treatment of neurodegenerative diseases related to RNA-binding proteins in the cell, e.g., amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
融合肉瘤（FUS）蛋白结合朊病毒样特性与多功能 DNA/RNA 结合域，并具有跨越 RNA 代谢调节的功能，包括转录、前体 mRNA 剪接、mRNA 运输和翻译。除了在 RNA 代谢中的作用外，FUS 还参与 DNA 完整性的维持。在这篇综述中，我们研究了 FUS 参与主要 DNA 修复途径的情况，重点关注与聚（ADP-核糖）化事件相关的 DNA 修复以及 FUS 与聚（ADP-核糖）的相互作用如何协调 DNA 链断裂的瞬时区室化。阐明朊病毒样 RNA 结合蛋白如何控制 DNA 修复途径，将加深我们对某些神经疾病和癌症发病机制的理解，并为开发相关创新治疗技术提供基础。这一知识还可能将聚（ADP-核糖）聚合酶抑制剂的应用范围扩展到治疗与细胞中 RNA 结合蛋白相关的神经退行性疾病，例如肌萎缩侧索硬化症和额颞叶痴呆。
