Institute of Molecular Biology gGmbH (IMB), Ackermannweg 4, Mainz D - 55128, Germany.
DNA Repair (Amst). 2023 Nov;131:103571. doi: 10.1016/j.dnarep.2023.103571. Epub 2023 Sep 16.
The actin cytoskeleton is of fundamental importance for numerous cellular processes, including intracellular transport, cell plasticity, and cell migration. However, functions of filamentous actin (F-actin) in the nucleus remain understudied due to the comparatively low abundance of nuclear actin and the resulting experimental limitations to its visualization. Owing to recent technological advances such as super-resolution microscopy and the development of nuclear-specific actin probes, essential roles of the actin cytoskeleton in the context of genome maintenance are now emerging. In addition to the contributions of monomeric actin as a component of multiple important nuclear protein complexes, nuclear actin has been found to undergo polymerization in response to DNA damage and DNA replication stress. Consequently, nuclear F-actin plays important roles in the regulation of intra-nuclear mobility of repair and replication foci as well as the maintenance of nuclear shape, two important aspects of efficient stress tolerance. Beyond actin itself, there is accumulating evidence for the participation of multiple actin-binding proteins (ABPs) in the surveillance of genome integrity, including nucleation factors and motor proteins of the myosin family. Here we summarize recent findings highlighting the importance of actin cytoskeletal factors within the nucleus in key genome maintenance pathways.
肌动蛋白细胞骨架对于许多细胞过程至关重要,包括细胞内运输、细胞可塑性和细胞迁移。然而,由于核内肌动蛋白的相对低丰度以及对其可视化的实验限制,丝状肌动蛋白(F-actin)在核内的功能仍未得到充分研究。由于最近的技术进步,如超分辨率显微镜和核特异性肌动蛋白探针的开发,肌动蛋白细胞骨架在基因组维持方面的重要作用正在显现。除了单体肌动蛋白作为多种重要核蛋白复合物的组成部分的贡献外,还发现核肌动蛋白在 DNA 损伤和 DNA 复制应激时会发生聚合。因此,核 F-actin 在调节修复和复制焦点在核内的流动性以及维持核形状方面发挥着重要作用,这是有效耐受应激的两个重要方面。除了肌动蛋白本身,越来越多的证据表明,多种肌动蛋白结合蛋白(ABPs)参与了基因组完整性的监测,包括核成核因子和肌球蛋白家族的动力蛋白。在这里,我们总结了最近的发现,强调了细胞核内肌动蛋白细胞骨架因子在关键基因组维持途径中的重要性。