Patching up the nucleus: a novel role for PMLII in nuclear envelope stability.

The nuclear envelope (NE) is important for cellular health as it protects and organizes the genome. NE dynamics are important for various cellular processes, including cell growth, migration, and removal of defective NE components. In extreme cases, the NE can rupture, followed by rapid repair to minimize damage to the genome. While our understanding of the repair process is increasing, a lot is still unknown about events leading up to NE rupture. Here, we found that promyelocytic leukemia protein isoform II (PMLII), a protein involved in nuclear PML body formation, forms condensates at the NE. PML condensates specifically form at sites where the lamina is disrupted, and two predicted amphipathic α-helices in the unique C-terminus of PMLII are essential for this localization. Live-cell imaging showed that when NE rupture occurs at these sites, the PMLII patch remains present until rupture repair is initiated. Using stable cell lines expressing FLAG-PMLII in a PML knockdown background, we found that PMLII caused an increase in the size of lamin holes without increasing the number of NE ruptures. We therefore hypothesize that PML patches play a role in NE integrity maintenance and dynamics through the stabilization of large holes in the lamina.