Shirt a Phobia

Sample Page

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 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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163029 – Ensembl, May 2017
  2. ^ a b c 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