Abstract
ABSTRACTThe nuclear pore complex (NPC) is the major conduit for nucleocytoplasmic transport and serves as a platform for gene regulation and DNA repair. Several nucleoporins undergo ubiquitylation and SUMOylation, and these modifications play an important role in nuclear pore dynamics and plasticity. Here, we perform a detailed analysis of these post-translational modifications of yeast nuclear basket proteins under normal growth conditions as well as upon cellular stresses, with a focus on SUMOylation. We find that the balance between the dynamics of SUMOylation and deSUMOylation of Nup60 and Nup2 at the NPC differs substantially, particularly in G1 and S phase. While Nup60 is the unique target of genotoxic stress within the nuclear basket that probably belongs to the SUMO-mediated DNA damage response pathway, both Nup2 and Nup60 show a dramatic increase in SUMOylation upon osmotic stress, with Nup2 SUMOylation being enhanced in Nup60 SUMO-deficient mutant yeast strains. Taken together, our data reveal that there are several levels of crosstalk between nucleoporins, and that the post-translational modifications of the NPC serve in sensing cellular stress signals.
Highlights
One of the defining features of a eukaryotic cell is the presence of membrane-enclosed organelles to carry out specialized functions
Nup60-small ubiquitin-related modifier (SUMO)-KR and the kinase-dead rad53K227R mutations showed additive growth defects upon genotoxic stress when combined in the same strain, indicating that Nup60 belongs to the SUMO-mediated DNA damage response pathway that is independent of the canonical DNA damage response (Fig. 1C)
We have previously reported that post-translational modifications of nuclear pore complex (NPC) proteins are important for its function in various nuclear processes
Summary
One of the defining features of a eukaryotic cell is the presence of membrane-enclosed organelles to carry out specialized functions. First observed in the 1950s as small dense regions dotting the NE, the NPCs are known to be massive megadalton-sized multiprotein assemblies that are embedded at points where the outer and inner nuclear membranes of the NE fuse. They comprise ∼30 nucleoporin proteins (Nups) that are arranged in multiple copies within defined subcomplexes, and there is evidence that the stability of these subcomplexes is higher than the supramolecular complex (Cronshaw et al, 2002; Rout et al, 2000; Schwartz, 2016). Nuclei of HeLa cells contain ∼3000 NPCs while yeast nuclei contain ∼100–200 NPCs
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