biostudies-literatureLampersberger LDeutsche Forschungsgemeinschaft (DFG)Cancer Research UKDeutsche ForschungsgemeinschaftUKRI | Medical Research Council (MRC)HHS | NIH | National Institute of General Medical SciencesWellcome TrustUKRI | Medical Research CouncilHHS | NIH | National Institute of General Medical Sciences (NIGMS)e2217992120https://www.ebi.ac.uk/biostudies/studies/S-EPMC9945973biostudies-literatureUnknown120(5)SWItch/sucrose non-fermenting (SWI/SNF) complexes are a family of chromatin remodelers that are conserved across eukaryotes. Mutations in subunits of SWI/SNF cause a multitude of different developmental disorders in humans, most of which have no current treatment options. Here, we identify an alanine-to-valine-causing mutation in the SWI/SNF subunit <i>snfc-5</i> (<i>SMARCB1</i> in humans) that prevents embryonic lethality in <i>Caenorhabditis elegans</i> nematodes harboring a loss-of-function mutation in the SWI/SNF subunit <i>swsn-1</i> (<i>SMARCC1/2</i> in humans). Furthermore, we found that the combination of this specific mutation in <i>snfc-5</i> and a loss-of-function mutation in either of the E3 ubiquitin ligases <i>ubr-5</i> (<i>UBR5</i> in humans) or <i>hecd-1</i> (<i>HECTD1</i> Proceedings of the National Academy of Sciences of the United States of AmericaLoss of the E3 ubiquitin ligases UBR-5 or HECD-1 restores <i>Caenorhabditis elegans</i> development in the absence of SWI/SNF function.PMC9945973259130777 -SFB 1177R01GM121597Epigenetics and EvolutionC13474/A27826219475/Z/19/ZMatus DQBeli PGhosh SPrice JConte FSarkies PXiao YLampersberger LBurton NOMiska EAJordan DfalseLoss of the E3 ubiquitin ligases UBR-5 or HECD-1 restores <i>Caenorhabditis elegans</i> development in the absence of SWI/SNF function.SWItch/sucrose non-fermenting (SWI/SNF) complexes are a family of chromatin remodelers that are conserved across eukaryotes. Mutations in subunits of SWI/SNF cause a multitude of different developmental disorders in humans, most of which have no current treatment options. Here, we identify an alanine-to-valine-causing mutation in the SWI/SNF subunit <i>snfc-5</i> (<i>SMARCB1</i> in humans) that prevents embryonic lethality in <i>Caenorhabditis elegans</i> nematodes harboring a loss-of-function mutation in the SWI/SNF subunit <i>swsn-1</i> (<i>SMARCC1/2</i> in humans). Furthermore, we found that the combination of this specific mutation in <i>snfc-5</i> and a loss-of-function mutation in either of the E3 ubiquitin ligases <i>ubr-5</i> (<i>UBR5</i> in humans) or <i>hecd-1</i> (<i>HECTD1</i> 2023-01-01T00:00:00Z2023 Jan2025-04-04T22:39:28.193Z2025-04-04T22:39:28.193ZS-EPMC99459733668965910.1073/pnas.2217992120