Article · Wikipedia archive · Last revised Jun 30, 2026

SMC6

Structural maintenance of chromosomes protein 6 is a protein that in humans is encoded by the SMC6 gene.

Last revised
Jun 30, 2026
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≈ 7 min
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Wikipedia ↗
SMC6
Identifiers
AliasesSMC6, SMC-6, SMC6L1, hstructural maintenance of chromosomes 6
External IDsOMIM: 609387; MGI: 1914491; HomoloGene: 41575; GeneCards: SMC6; OMA:SMC6 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

79677

67241

Ensembl

ENSG00000163029

ENSMUSG00000020608

UniProt

Q96SB8

Q924W5

RefSeq (mRNA)

NM_001142286
NM_024624

NM_025695
NM_001324476
NM_001361252

RefSeq (protein)

NP_001135758
NP_078900

NP_001311405
NP_079971
NP_001348181

Location (UCSC)Chr 2: 17.66 – 17.8 MbChr 12: 11.32 – 11.37 Mb
PubMed search34
Wikidata
View/Edit HumanView/Edit Mouse

Structural maintenance of chromosomes protein 6 is a protein that in humans is encoded by the SMC6 gene.56

Structure

The SMC6 was discovered first in fission yeast as RAD18 (SMC6). It forms a heterodimeric complex with Spr18 (SMC5) protein.78 In yeast, SMC5/6 complex has sub-units which consists of SMC5, SMC6 and six nonstructural maintenance of chromosomes (NSE) proteins. Nse1-Nse3-Nse4 subunits bridge the Smc5 head Smc6 and allow the binding of DNA.91011

It is potentially involved in the Alternative lengthening of telomeres cancer mechanism.12

This depicts the placement of Nse proteins along the SMC5/6 complex in budding and fission yeast. This image does not include Nse2, as its position in the complex is not currently known. source ↗

Nse subunits

Nse1-Nse3-Nse4 subunits bridge the heads of the Smc5 and Smc6 proteins and allow the complex to bind DNA. Nse5 and Nse6 form a sub-complex which localizes to the head of the SMC5/6 complex in the budding yeast Saccharomyces cerevisiae, and to the hinges of the SMC5/6 complex in the fission yeast Schizosaccharomyces pombe. The Nse5/6 sub-complex is required for the replication of S. cerevisiae, but has not been characterized as essential in S. pombe. Orthologous proteins to Nse5-Nse6 exist in other eukaryotes, namely ASAP1-SNI1 in Arabidopsis thaliana and SLF1-SLF2 in humans, which are believed have similar function to their Nse counterparts. The localization of SLF1 and SLF2 on the human SMC5/6 complex is unknown.1314

Localization

The Smc5/6 complex has localization methods which are not heavily conserved. In humans the complex is localized to viral DNA sequences using SMC5/6 localization factors 1 and 2 (SLF1 and SLF2) which contributes to viral resistance.15 In the plant A. thaliana, this heterodimer can be localized to double stranded breaks for homologous recombination using the SWI3B complex of the SWI/SNF pathway.16 Once localized to the DNA, the SCM5/6 complex non-specifically binds to ~20 DNA base pairs.17

Role in recombination and meiosis

Smc6 and Smc5 proteins form a heterodimeric ring-like structure and together with other non-SMC elements form the SMC-5/6 complex. In the worm Caenorhabditis elegans this complex interacts with the HIM-6(BLM) helicase to promote meiotic recombination intermediate processing and chromosome maturation.18 The SMC-5/6 complex in mouse oocytes is essential for the formation of segregation competent bivalents during meiosis.19 In the yeast Saccharomyces cerevisiae, SMC6 is necessary for resistance to DNA damage as well as for damage-induced interchromosomal and sister chromatid recombination.20 In humans, a chromosome breakage syndrome characterized by severe lung disease in early childhood is associated with a mutation in a component of the SMC-5/6 complex.21 Patient's cells display chromosome rearrangements, micronuclei, sensitivity to DNA damage and defective homologous recombination.

References

References

  1. GRCh38: Ensembl release 89: ENSG00000163029 – Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000020608 – Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–435. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
  6. "Entrez Gene: SMC6 structural maintenance of chromosomes 6".
  7. Fousteri MI, Lehmann AR (April 2000). "A novel SMC protein complex in Schizosaccharomyces pombe contains the Rad18 DNA repair protein". The EMBO Journal. 19 (7): 1691–1702. doi:10.1093/emboj/19.7.1691. PMC 310237. PMID 10747036.
  8. Lehmann AR, Walicka M, Griffiths DJ, Murray JM, Watts FZ, McCready S, et al. (December 1995). "The rad18 gene of Schizosaccharomyces pombe defines a new subgroup of the SMC superfamily involved in DNA repair". Molecular and Cellular Biology. 15 (12): 7067–7080. doi:10.1128/mcb.15.12.7067. PMC 230962. PMID 8524274.
  9. Palecek J, Vidot S, Feng M, Doherty AJ, Lehmann AR (December 2006). "The Smc5-Smc6 DNA repair complex: bridging of the Smc5-Smc6 heads by the KLEISIN, Nse4, and non-Kleisin subunits". The Journal of Biological Chemistry. 281 (48): 36952–36959. doi:10.1074/jbc.M608004200. PMID 17005570.
  10. Zabrady K, Adamus M, Vondrova L, Liao C, Skoupilova H, Novakova M, et al. (February 2016). "Chromatin association of the SMC5/6 complex is dependent on binding of its NSE3 subunit to DNA". Nucleic Acids Research. 44 (3): 1064–1079. doi:10.1093/nar/gkv1021. PMC 4756808. PMID 26446992.
  11. Vondrova L, Kolesar P, Adamus M, Nociar M, Oliver AW, Palecek JJ (June 2020). "A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6". Scientific Reports. 10 (1) 9694. Bibcode:2020NatSR..10.9694V. doi:10.1038/s41598-020-66647-w. PMC 7297730. PMID 32546830.
  12. Potts PR, Yu H (2007). "The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins". Nature Structural & Molecular Biology. 14 (7): 581–590. doi:10.1038/nsmb1259. PMID 17589526. S2CID 7915836.
  13. Yan S, Wang W, Marqués J, Mohan R, Saleh A, Durrant WE, et al. (November 2013). "Salicylic acid activates DNA damage responses to potentiate plant immunity". Molecular Cell. 52 (4): 602–610. doi:10.1016/j.molcel.2013.09.019. PMC 3863363. PMID 24207055.
  14. Diaz M, Pecinka A (January 2018). "Scaffolding for Repair: Understanding Molecular Functions of the SMC5/6 Complex". Genes. 9 (1). Basel: 36. doi:10.3390/genes9010036. PMC 5793187. PMID 29329249.
  15. Oravcová M, Nie M, Zilio N, Maeda S, Jami-Alahmadi Y, Lazzerini-Denchi E, et al. (November 2022). Chiolo IE, Tyler JK (eds.). "The Nse5/6-like SIMC1-SLF2 complex localizes SMC5/6 to viral replication centers". eLife. 11 e79676. doi:10.7554/eLife.79676. PMC 9708086. PMID 36373674.
  16. Jiang J, Mao N, Hu H, Tang J, Han D, Liu S, et al. (July 2019). "A SWI/SNF subunit regulates chromosomal dissociation of structural maintenance complex 5 during DNA repair in plant cells". Proceedings of the National Academy of Sciences of the United States of America. 116 (30): 15288–15296. Bibcode:2019PNAS..11615288J. doi:10.1073/pnas.1900308116. PMC 6660752. PMID 31285327.
  17. Yu Y, Li S, Ser Z, Kuang H, Than T, Guan D, et al. (June 2022). "Cryo-EM structure of DNA-bound Smc5/6 reveals DNA clamping enabled by multi-subunit conformational changes". Proceedings of the National Academy of Sciences of the United States of America. 119 (23) e2202799119. Bibcode:2022PNAS..11902799Y. doi:10.1073/pnas.2202799119. PMC 9191643. PMID 35648833.
  18. Hong Y, Sonneville R, Agostinho A, Meier B, Wang B, Blow JJ, et al. (2016). "The SMC-5/6 Complex and the HIM-6 (BLM) Helicase Synergistically Promote Meiotic Recombination Intermediate Processing and Chromosome Maturation during Caenorhabditis elegans Meiosis". PLoS Genetics. 12 (3) e1005872. doi:10.1371/journal.pgen.1005872. PMC 4807058. PMID 27010650.
  19. Hwang G, Sun F, O'Brien M, Eppig JJ, Handel MA, Jordan PW (2017). "SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes". Development. 144 (9). Cambridge, England: 1648–1660. doi:10.1242/dev.145607. PMC 5450844. PMID 28302748.
  20. Onoda F, Takeda M, Seki M, Maeda D, Tajima J, Ui A, et al. (2004). "SMC6 is required for MMS-induced interchromosomal and sister chromatid recombinations in Saccharomyces cerevisiae". DNA Repair. 3 (4). Amst: 429–439. doi:10.1016/j.dnarep.2003.12.007. PMID 15010319.
  21. van der Crabben SN, Hennus MP, McGregor GA, Ritter DI, Nagamani SC, Wells OS, et al. (2016). "Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease". The Journal of Clinical Investigation. 126 (8): 2881–2892. doi:10.1172/JCI82890. PMC 4966312. PMID 27427983.
Further reading

Further reading