Abstract:
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.
摘要:
转运(ESCRT)机制所需的内体分选复合物由在多个细胞位点组装的蛋白质的关节结构组成。ESCRT机制涉及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。ESCRTI综合体的子单元主要负责将机械锚定到行动地点。ESCRTII亚基的功能是桥接和招募ESCRTIII亚基。后者负责完成以下操作,独立于行动地点,涉及膜边缘的修复和融合。在这次审查中,我们报告了与ESCRT机制在两个位置的活性相关的数据:核膜和中体以及在胞质分裂的最后阶段连接细胞的桥。在这些背景下,该机制通过有助于控制脱落检查点以及核包膜重组和相关弹性,在保护基因组完整性方面发挥着重要作用。始终如一,一些研究表明,ESCRT机制的功能障碍如何导致基因组损伤,并且是病理的共同驱动因素,如层粘连蛋白病和癌症。