ArticleThe Journal of clinical investigation2014
Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
65 citing papers in PubMed, 110 citations in OpenAlex.
- NSMCE2 / MMS21 structural variant causes chromosome breakage syndrome with primordial dwarfism and severe lung disease.European journal of human genetics : EJHG · 2026Article
- The Multifunctional SMC5/6 Complex in Genome Stability, Antiviral Restriction, and Human Disease.Current issues in molecular biology · 2026Review
- Ligase-dependent and independent functions of the C-terminus of Mms21 contribute to optimal growth and genome stability inMolecular biology of the cell · 2026Article
- Disruption of the structural maintenance of chromosomes 5/6 complex enables tumor mutagenesis.NAR cancer · 2026Article
- Molecular determinants of Smc5/6 association with DNA junctions.Nature communications · 2026Article
- Article
- Whole-genome sequencing reveals patterns of runs of homozygosity underlying genetic diversity and selection in domestic rabbits.BMC genomics · 2025Article
- A stress-dependent TDP-43 SUMOylation program preserves neuronal function.Molecular neurodegeneration · 2025Article
- Positive Selection Drives the Evolution of the Structural Maintenance of Chromosomes (SMC) Complexes.Genes · 2024Article
- The SMC5/6 complex prevents genotoxicity upon APOBEC3A-mediated replication stress.The EMBO journal · 2024Article
- NFATC2IP is a mediator of SUMO-dependent genome integrity.Genes & development · 2024Article
- The SMC5/6 complex: folding chromosomes back into shape when genomes take a break.Nucleic acids research · 2024Review
- SMC5/6 Promotes Replication Fork Stability via Negative Regulation of the COP9 Signalosome.International journal of molecular sciences · 2024Article
- Article
- Large-scale phenogenomic analysis of human cancers uncovers frequent alterations affecting SMC5/6 complex components in breast cancer.NAR cancer · 2023Article
- A sterol-PI(4)P exchanger modulates the Tel1/ATM axis of the DNA damage response.The EMBO journal · 2023Article
- Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size.Cells · 2023Review
- Heterogeneity in susceptibility to polycystic ovary syndrome among women with epilepsy.Acta epileptologica · 2023Article
- The multi-functional Smc5/6 complex in genome protection and disease.Nature structural & molecular biology · 2023Review
- Bioinformatics Analysis of Next Generation Sequencing Data Identifies Molecular Biomarkers Associated With Type 2 Diabetes Mellitus.Clinical medicine insights. Endocrinology and diabetes · 2023Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 1 institution in 2 countries.
Funding
Abstract
Structural maintenance of chromosomes (SMC) complexes are essential for maintaining chromatin structure and regulating gene expression. Two the three known SMC complexes, cohesin and condensin, are important for sister chromatid cohesion and condensation, respectively; however, the function of the third complex, SMC5-6, which includes the E3 SUMO-ligase NSMCE2 (also widely known as MMS21) is less clear. Here, we characterized 2 patients with primordial dwarfism, extreme insulin resistance, and gonadal failure and identified compound heterozygous frameshift mutations in NSMCE2. Both mutations reduced NSMCE2 expression in patient cells. Primary cells from one patient showed increased micronucleus and nucleoplasmic bridge formation, delayed recovery of DNA synthesis, and reduced formation of foci containing Bloom syndrome helicase (BLM) after hydroxyurea-induced replication fork stalling. These nuclear abnormalities in patient dermal fibroblast were restored by expression of WT NSMCE2, but not a mutant form lacking SUMO-ligase activity. Furthermore, in zebrafish, knockdown of the NSMCE2 ortholog produced dwarfism, which was ameliorated by reexpression of WT, but not SUMO-ligase-deficient NSMCE. Collectively, these findings support a role for NSMCE2 in recovery from DNA damage and raise the possibility that loss of its function produces dwarfism through reduced tolerance of replicative stress.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.