SUMO in the regulation of DNA repair and transcription at nuclear pores

Abstract

Two related post‐translational modifications, the covalent linkage of Ubiquitin and the Small Ubiquitin‐related MOdifier (SUMO) to lysine residues, play key roles in the regulation of both DNA repair pathway choice and transcription. Whereas ubiquitination is generally associated with protein degradation, the impact of sumoylation has been more mysterious. Sumoylation effects are largely mediated by the subnuclear localization of its targets, particularly in response to DNA damage. This is governed in part by the concentration of SUMO protease at nuclear pores (1,2). We review here the roles of sumoylation in determining subnuclear locus positioning relative to the nuclear envelope and the nuclear envelope to facilitate repair and to regulate transcription.

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma

“…Furthermore, while our data suggests TAK-981 disruption of several motifs involved in DNA repair are downregulated following TAK-981 treatment, which may be the direct link to the DNA damage seen following BAF complex redistribution. While our data indicate that this is at least in part due to the rebalancing of BAF complexes, SUMOylation plays a direct role in the DNA damage response through other targets of SUMOylation (Claessens et al, 2023;Gasser and Stutz, 2023). Thus, further studies are needed to better characterize the mechanism of DNA damage following TAK-981 treatment in SS.…”

Molecular Organization and Regulation of the Mammalian Synapse by the Post-Translational Modification SUMOylation

“…The physiology and physiopathology associated with the equilibrium between the SUMOylation and deSUMOylation of nuclear proteins has been extensively reviewed [ 74 , 75 ], but several proteins are also SUMO-modified in extranuclear compartments in neurons [ 6 , 7 , 8 , 9 ]. However, given the low proportion of SUMOylation outside of the nucleus and the high SUMO protease activities [ 76 ], identification of SUMOylated proteins in other subcellular compartments and especially at synapses remains particularly challenging.…”

Targeted protein degradation of the CPSF complex by benzoxaboroles through sumoylation

“…SUMO is important for translocation of mRNA to the NPC in animals and fungal cells (Gasser and Stutz 2023), and while not demonstrated experimentally, there is sufficient conservation within trypanosomes to expect that similar mechanisms operate.…”

“…Significantly, the ESB contains multiple proteins responsible for securing monoallelic expression of VSG, while sumoylation is associated with proteins located at VSG-encoding chromatin (Saura et al, 2019). SUMO is important for translocation of mRNA to the NPC in animals and fungal cells (Gasser and Stutz 2023), and while not demonstrated experimentally, there is sufficient conservation within trypanosomes to expect that similar mechanisms operate.…”