SMC6

SMC6

SMC6

Protein-coding gene in the species Homo sapiens

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

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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 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.

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.[13][14]

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

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    GRCh38: Ensembl release 89: ENSG00000163029 – Ensembl, May 2017
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    "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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    "Entrez Gene: SMC6 structural maintenance of chromosomes 6".
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    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.
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    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.
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    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.
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    Diaz, Mariana; Pecinka, Ales (2018-01-12). "Scaffolding for Repair: Understanding Molecular Functions of the SMC5/6 Complex". Genes. 9 (1): 36. doi:10.3390/genes9010036. ISSN 2073-4425. PMC 5793187. PMID 29329249.
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    Oravcová, Martina; Nie, Minghua; Zilio, Nicola; Maeda, Shintaro; Jami-Alahmadi, Yasaman; Lazzerini-Denchi, Eros; Wohlschlegel, James A; Ulrich, Helle D; Otomo, Takanori; Boddy, Michael N (2022-11-14). Chiolo, Irene E; Tyler, Jessica K (eds.). "The Nse5/6-like SIMC1-SLF2 complex localizes SMC5/6 to viral replication centers". eLife. 11: e79676. doi:10.7554/eLife.79676. ISSN 2050-084X. PMC 9708086. PMID 36373674.
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