Understanding how the integrity of the nuclear membranes is protected against internal and external stresses is an emergent challenge. Work reviewed here investigated the mechanisms by which losses of nuclear-cytoplasmic compartmentalization are sensed and ameliorated. Fundamental to these is spatial control over interactions between the endosomal sorting complexes required for transport machinery and LAP2-emerin-MAN1 family inner nuclear membrane proteins, which together promote nuclear envelope sealing in interphase and at the end of mitosis. We suggest that the size of the nuclear envelope hole dictates the mechanism of its repair, with larger holes requiring barrier-to-autointegration factor and the potential triggering of a postmitotic nuclear envelope reassembly pathway in interphase. We also consider why these mechanisms fail at ruptured micronuclei. Together, this work re-emphasizes the need to understand how membrane flow and local lipid metabolism help ensure that the nuclear envelope is refractory to mechanical rupture yet fluid enough to allow its essential dynamics.

中文翻译：

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维修冠军：关于感知和维修核包膜屏障的新兴观点。

理解如何保护核膜的完整性免受内部和外部压力是一个新的挑战。这里审查的工作调查了感官和减轻核细胞质区室化损失的机制。这些的基础是对运输机械所需的内体分选复合物与LAP2-emerin-MAN1家族内核膜蛋白之间相互作用的空间控制，LAP2-emerin-MAN1家族内核膜蛋白共同促进相间和有丝分裂末期的核膜封闭。我们认为，核包膜孔的大小决定了其修复机制，较大的孔需要屏障自整合因子，并可能在相间触发有丝分裂后核包膜重组途径。我们还考虑了为什么这些机制在微核破裂时失败。总之，这项工作再次强调了了解膜流动和局部脂质代谢如何帮助确保核膜对机械破裂是难熔的，但具有足够的流动性以允许其基本动力学的需求。