| Full Name | Structural Maintenance of Chromosomes 3 |
|---|---|
| Symbol | SMC3 |
| Chromosomal Location | 10q25.2 |
| NCBI Gene ID | [9126](https://www.ncbi.nlm.nih.gov/gene/9126) |
| OMIM | [606062](https://omim.org/entry/606062) |
| Ensembl ID | [ENSG00000103052](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000103052) |
| UniProt | [Q9UQE7](https://www.uniprot.org/uniprot/Q9UQE7) |
| Associated Diseases | Cornelia de Lange Syndrome, Cohesinopathy, [Cancer](/cancer) |
SMC3 (Structural Maintenance of Chromosomes 3) is a core subunit of the cohesin complex, a multi-protein ring structure essential for sister chromatid cohesion, DNA repair, and three-dimensional genome organization. Cohesin, composed of SMC1A, SMC3, RAD21, and SA1/SA2, topologically embraces DNA to regulate chromosome dynamics throughout the cell cycle[1]. In post-mitotic neurons, cohesin plays critical roles in gene regulation, DNA damage response, and maintenance of genomic stability.
SMC3 forms one arm of the cohesin ring, dimerizing with SMC1A through their hinge domains to create a V-shaped structure that, together with RAD21 bridging the ATPase head domains, encircles chromosomal DNA[2]. The SMC3 ATPase head domain hydrolyzes ATP to drive conformational changes that regulate cohesin loading, translocation, and release from chromatin.
During S phase, the cohesin complex establishes cohesion between newly replicated sister chromatids, maintaining their association until anaphase onset. This cohesion is essential for accurate chromosome segregation and prevention of aneuploidy[3]. ESCO1 and ESCO2 acetyltransferases modify SMC3 to stabilize cohesive interactions.
In neurons and other post-mitotic cells, cohesin participates in:
Cohesin is recruited to DNA double-strand breaks where it promotes:
Heterozygous SMC3 mutations cause approximately 1-2% of CdLS cases, a multisystem developmental disorder characterized by:
SMC3-related CdLS typically presents with milder features compared to NIPBL mutations but with similar mechanistic basis involving disrupted cohesin function.
SMC3 variants are associated with:
Cohesin mutations, including SMC3 alterations, occur in various cancers:
Dysregulated cohesin function may contribute to oncogenic transcriptional programs and genomic instability[8].
SMC3 is ubiquitously expressed across tissues, with particularly high expression in:
In mature neurons, SMC3 expression persists, reflecting ongoing roles in chromatin organization and gene regulation rather than cell division[9].
SMC3 shows moderate, widespread expression throughout the adult human brain, with slightly elevated levels in:
Therapeutic strategies for cohesinopathies focus on:
SMC3 and cohesin represent potential therapeutic targets in malignancies:
Nasmyth K, Haering CH. Cohesin: its roles and mechanisms. Annual Review of Genetics. 2009. ↩︎
Higashi TL, et al. A structure-based mechanism for cohesin loading onto chromosomes. Nature. 2020. ↩︎
Michaelis C, Ciosk R, Nasmyth K. [Cohesins: chromosomal proteins that prevent premature separation of sister chromatids](https://doi.org/10.1016/s0092-8674(01). Cell. 1997. ↩︎
Rao SSP, et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014. ↩︎
Watrin E, Peters JM. The cohesin complex is required for the DNA damage-induced G2/M checkpoint. Molecular Cell. 2006. ↩︎
Deardorff MA, et al. SMC3 mutations in Cornelia de Lange syndrome. American Journal of Human Genetics. 2007. ↩︎
Gomperts SN, et al. Cornelia de Lange syndrome and autism spectrum disorder. American Journal of Medical Genetics Part A. 2009. ↩︎
Kon A, et al. Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. Nature Genetics. 2013. ↩︎
Wendt KS, et al. Cohesin mediates transcriptional insulation of CCCTC-binding factor. Nature. 2008. ↩︎
Kline AD, et al. Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement. Nature Reviews Genetics. 2018. ↩︎