SMC6

SMC6
Identifiers
Aliases	SMC6, SMC-6, SMC6L1, hstructural maintenance of chromosomes 6
External IDs	OMIM: 609387 MGI: 1914491 HomoloGene: 41575 GeneCards: SMC6
Gene location (Human)
Chr.	Chromosome 2 (human)
End	17,800,242 bp
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)
End	11,369,786 bp
RNA expression pattern
	Top expressed in
	retinal pigment epithelium; ; testicle; ; Achilles tendon; ; lung; ; caput epididymis; ; heart; ; corpus callosum; ; kidney;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	nucleotide binding; GO:0001948 protein binding; ATP binding; ubiquitin protein ligase binding;
Cellular component	site of double-strand break; PML body; sex chromosome; nuclear speck; Smc5-Smc6 complex; intracellular anatomical structure; nucleoplasm; chromosome; chromosome, telomeric region; interchromatin granule; nucleus;
Biological process	DNA recombination; cellular response to DNA damage stimulus; telomere maintenance via recombination; cellular senescence; positive regulation of chromosome segregation; double-strand break repair via homologous recombination; DNA repair;
	Sources:Amigo / QuickGO
Orthologs
	79677
	67241
	ENSG00000163029
	ENSMUSG00000020608
	Q96SB8
	Q924W5
	NM_001142286; NM_024624
	NM_025695; NM_001324476; NM_001361252
	NP_001135758; NP_078900
	NP_001311405; NP_079971; NP_001348181
	Wikidata
View/Edit Human	View/Edit Mouse

SMC6
Identifiers
Aliases	SMC6, SMC-6, SMC6L1, hstructural maintenance of chromosomes 6
External IDs	OMIM: 609387 MGI: 1914491 HomoloGene: 41575 GeneCards: SMC6
Gene location (Human)
Chr.	Chromosome 2 (human)
End	17,800,242 bp
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)
End	11,369,786 bp
RNA expression pattern
	Top expressed in
	retinal pigment epithelium; ; testicle; ; Achilles tendon; ; lung; ; caput epididymis; ; heart; ; corpus callosum; ; kidney;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	nucleotide binding; GO:0001948 protein binding; ATP binding; ubiquitin protein ligase binding;
Cellular component	site of double-strand break; PML body; sex chromosome; nuclear speck; Smc5-Smc6 complex; intracellular anatomical structure; nucleoplasm; chromosome; chromosome, telomeric region; interchromatin granule; nucleus;
Biological process	DNA recombination; cellular response to DNA damage stimulus; telomere maintenance via recombination; cellular senescence; positive regulation of chromosome segregation; double-strand break repair via homologous recombination; DNA repair;
	Sources:Amigo / QuickGO
Orthologs
	79677
	67241
	ENSG00000163029
	ENSMUSG00000020608
	Q96SB8
	Q924W5
	NM_001142286; NM_024624
	NM_025695; NM_001324476; NM_001361252
	NP_001135758; NP_078900
	NP_001311405; NP_079971; NP_001348181
	Wikidata
View/Edit Human	View/Edit Mouse

Structural maintenance of chromosomes protein 6 is a protein that in humans is encoded by the SMC6 gene.^[5]^[6]

Structure[]

The SMC6 was discovered first in fission yeast as RAD18 (SMC6). It forms a heterodimeric complex with Spr18 (SMC5) protein.^[7]^[8] 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. ^[9]^[10]^[11]

It is involved in the Alternative lengthening of telomeres cancer mechanism.^[14]

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.^[15] The SMC-5/6 complex in mouse oocytes is essential for the formation of segregation competent bivalents during meiosis.^[16] In the yeast Saccharomyces cerevisiae, SMC6 is necessary for resistance to DNA damage as well as for damage-induced interchromosomal and sister chromatid recombination.^[17] 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.^[18] Patient’s cells display chromosome rearrangements, micronuclei, sensitivity to DNA damage and defective homologous recombination.

References[]

^ ^a ^b ^c ^d ^e ^f GRCh38: Ensembl release 89: ENSG00000163029 - Ensembl, May 2017
^ ^a ^b ^c ^d ^e ^f GRCm38: Ensembl release 89: ENSMUSG00000020608 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
^ "Entrez Gene: SMC6 structural maintenance of chromosomes 6".
^ 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): 1691–702. doi:10.1093/emboj/19.7.1691. PMC 310237. PMID 10747036.
^ Lehmann AR, Walicka M, Griffiths DJ, Murray JM, Watts FZ, McCready S, Carr AM (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): 7067–80. doi:10.1128/mcb.15.12.7067. PMC 230962. PMID 8524274.
^ 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.
^ Zabrady K, Adamus M, Vondrova L, Liao C, Skoupilova H, Novakova M, Jurcisinova L, Alt A, Oliver AW, Lehmann AR, Palecek JJ (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.
^ 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.
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Potts PR, Yu H (2007). "The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins". Nat. Struct. Mol. Biol. 14 (7): 581–90. doi:10.1038/nsmb1259. PMID 17589526. S2CID 7915836.
^ Hong Y, Sonneville R, Agostinho A, Meier B, Wang B, Blow JJ, Gartner A (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 Genet. 12 (3): e1005872. doi:10.1371/journal.pgen.1005872. PMC 4807058. PMID 27010650.
^ 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): 1648–1660. doi:10.1242/dev.145607. PMC 5450844. PMID 28302748.
^ Onoda F, Takeda M, Seki M, Maeda D, Tajima J, Ui A, Yagi H, Enomoto T (2004). "SMC6 is required for MMS-induced interchromosomal and sister chromatid recombinations in Saccharomyces cerevisiae". DNA Repair (Amst.). 3 (4): 429–39. doi:10.1016/j.dnarep.2003.12.007. PMID 15010319.
^ van der Crabben SN, Hennus MP, McGregor GA, Ritter DI, Nagamani SC, Wells OS, Harakalova M, Chinn IK, Alt A, Vondrova L, Hochstenbach R, van Montfrans JM, Terheggen-Lagro SW, van Lieshout S, van Roosmalen MJ, Renkens I, Duran K, Nijman IJ, Kloosterman WP, Hennekam E, Orange JS, van Hasselt PM, Wheeler DA, Palecek JJ, Lehmann AR, Oliver AW, Pearl LH, Plon SE, Murray JM, van Haaften G (2016). "Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease". J. Clin. Invest. 126 (8): 2881–92. doi:10.1172/JCI82890. PMC 4966312. PMID 27427983.

Further reading[]

Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
Taylor EM, Moghraby JS, Lees JH, et al. (2001). "Characterization of a novel human SMC heterodimer homologous to the Schizosaccharomyces pombe Rad18/Spr18 complex". Mol. Biol. Cell. 12 (6): 1583–94. doi:10.1091/mbc.12.6.1583. PMC 37326. PMID 11408570.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature. 434 (7034): 724–31. Bibcode:2005Natur.434..724H. doi:10.1038/nature03466. PMID 15815621.
Potts PR, Yu H (2005). "Human MMS21/NSE2 is a SUMO ligase required for DNA repair". Mol. Cell. Biol. 25 (16): 7021–32. doi:10.1128/MCB.25.16.7021-7032.2005. PMC 1190242. PMID 16055714.
Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
Potts PR, Porteus MH, Yu H (2006). "Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks". EMBO J. 25 (14): 3377–88. doi:10.1038/sj.emboj.7601218. PMC 1523187. PMID 16810316.

This article on a gene on human chromosome 2 is a stub. You can help Wikipedia by .

[refGRCh38Ensembl-1] ^ ^a ^b ^c ^d ^e ^f GRCh38: Ensembl release 89: ENSG00000163029 - Ensembl, May 2017

[refGRCm38Ensembl-2] ^ ^a ^b ^c ^d ^e ^f 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.

[pmid11230166-5] Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.

[entrez-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): 1691–702. doi:10.1093/emboj/19.7.1691. PMC 310237. PMID 10747036.

[8] Lehmann AR, Walicka M, Griffiths DJ, Murray JM, Watts FZ, McCready S, Carr AM (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): 7067–80. 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, Jurcisinova L, Alt A, Oliver AW, Lehmann AR, Palecek JJ (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] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[13] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Potts2007-14] Potts PR, Yu H (2007). "The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins". Nat. Struct. Mol. Biol. 14 (7): 581–90. doi:10.1038/nsmb1259. PMID 17589526. S2CID 7915836.

[pmid27010650-15] Hong Y, Sonneville R, Agostinho A, Meier B, Wang B, Blow JJ, Gartner A (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 Genet. 12 (3): e1005872. doi:10.1371/journal.pgen.1005872. PMC 4807058. PMID 27010650.

[pmid28302748-16] 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): 1648–1660. doi:10.1242/dev.145607. PMC 5450844. PMID 28302748.

[pmid15010319-17] Onoda F, Takeda M, Seki M, Maeda D, Tajima J, Ui A, Yagi H, Enomoto T (2004). "SMC6 is required for MMS-induced interchromosomal and sister chromatid recombinations in Saccharomyces cerevisiae". DNA Repair (Amst.). 3 (4): 429–39. doi:10.1016/j.dnarep.2003.12.007. PMID 15010319.

[pmid27427983-18] van der Crabben SN, Hennus MP, McGregor GA, Ritter DI, Nagamani SC, Wells OS, Harakalova M, Chinn IK, Alt A, Vondrova L, Hochstenbach R, van Montfrans JM, Terheggen-Lagro SW, van Lieshout S, van Roosmalen MJ, Renkens I, Duran K, Nijman IJ, Kloosterman WP, Hennekam E, Orange JS, van Hasselt PM, Wheeler DA, Palecek JJ, Lehmann AR, Oliver AW, Pearl LH, Plon SE, Murray JM, van Haaften G (2016). "Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease". J. Clin. Invest. 126 (8): 2881–92. doi:10.1172/JCI82890. PMC 4966312. PMID 27427983.

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