Department of Biology and Biotechnologies "Charles Darwin", Sapienza University, 00185 Rome, Italy.
CNR Institute of Molecular Biology and Pathology, 00185 Rome, Italy.
Cells. 2024 Aug 5;13(15):1307. doi: 10.3390/cells13151307.
The endosomal sorting complex required for transport (ESCRT) machinery is composed of an articulated architecture of proteins that assemble at multiple cellular sites. The ESCRT machinery is involved in pathways that are pivotal for the physiology of the cell, including vesicle transport, cell division, and membrane repair. The subunits of the ESCRT I complex are mainly responsible for anchoring the machinery to the action site. The ESCRT II subunits function to bridge and recruit the ESCRT III subunits. The latter are responsible for finalizing operations that, independently of the action site, involve the repair and fusion of membrane edges. In this review, we report on the data related to the activity of the ESCRT machinery at two sites: the nuclear membrane and the midbody and the bridge linking cells in the final stages of cytokinesis. In these contexts, the machinery plays a significant role for the protection of genome integrity by contributing to the control of the abscission checkpoint and to nuclear envelope reorganization and correlated resilience. Consistently, several studies show how the dysfunction of the ESCRT machinery causes genome damage and is a codriver of pathologies, such as laminopathies and cancer.
内体分选复合物运输所需（ESCRT）机械由蛋白质的连接结构组成，这些蛋白质在多个细胞部位组装。ESCRT 机械参与了对细胞生理学至关重要的途径，包括囊泡运输、细胞分裂和膜修复。ESCRT I 复合物的亚基主要负责将机械固定在作用部位。ESCRT II 亚基的功能是桥接和招募 ESCRT III 亚基。后者负责完成独立于作用部位的膜边缘修复和融合的操作。在这篇综述中，我们报告了与 ESCRT 机械在两个部位的活性相关的数据：核膜和中期体以及在胞质分裂的最后阶段连接细胞的桥梁。在这些情况下，该机械通过有助于控制分裂检查点和核膜重组以及相关的弹性，为保护基因组完整性发挥了重要作用。一致地，几项研究表明 ESCRT 机械的功能障碍如何导致基因组损伤，并成为疾病的共同驱动因素，如层粘连蛋白病和癌症。
