SMC5

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SMC5
Identifiers
AliasesSMC5, SMC5L1, structural maintenance of chromosomes 5
External IDsOMIM: 609386 MGI: 2385088 HomoloGene: 41009 GeneCards: SMC5
Orthologs
SpeciesHumanMouse
Entrez

23137

226026

Ensembl

ENSG00000198887

ENSMUSG00000024943

UniProt

Q8IY18

Q8CG46

RefSeq (mRNA)

NM_015110

NM_001252684
NM_001252685
NM_153808

RefSeq (protein)

NP_055925

NP_001239613
NP_001239614
NP_722503

Location (UCSC)Chr 9: 70.26 – 70.35 MbChr 19: 23.18 – 23.25 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structural maintenance of chromosomes protein 5 is a protein encoded by the SMC5 gene in human.[5][6]

The structural maintenance of chromosomes' complex underlying mechanisms involved in the dynamics of chromatin dynamics is unknown, and new discoveries are shedding light on the various functions.[7] The SMC complex mediates long-distance interactions that enable higher-order folding of chromatin in interphase. The SMC complex has an ATPase activity, a conserved kleisin, as well as regulatory subunits.[7] SMC protein complexes are involved in DNA repair, transcriptional pathways, regulation of chromosome segregation, and immunity in Arabidopsis. In eukaryotes the structural maintenance chromosomes consists of cohesin (SMC1 AND SMC3), condensin (SMC2 and SMC4), and SMC5/6 complexes.

Structure[edit]

The Smc5/6 complex was discovered in fission yeast. RAD18 (SMC6), the DNA damage gene in fission yeast, also encodes an SMC-like protein and forms a heterodimeric complex with Spr18 (SMC5) protein.[8][9] 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.[10][11][12]

It is involved in the Alternative lengthening of telomeres cancer mechanism.[13][14]

Nse subunits[edit]

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.[15][16]

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.

Localization in different organisms[edit]

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.[17] 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.[18] Once localized to the DNA, the SCM5/6 complex non-specifically binds to ~20 DNA base pairs[19]

Role in recombination and meiosis[edit]

Smc5 and Smc6 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.[20] The SMC-5/6 complex in mouse oocytes is essential for the formation of segregation competent bivalents during meiosis.[21] 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.[22] Patient's cells display chromosome rearrangements, micronuclei, sensitivity to DNA damage and defective homologous recombination.

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000198887 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024943 – 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. ^ Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (February 1998). "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Research. 5 (1): 31–9. doi:10.1093/dnares/5.1.31. PMID 9628581.
  6. ^ "Entrez Gene: SMC5 structural maintenance of chromosomes 5".
  7. ^ a b Jeppsson K, Kanno T, Shirahige K, Sjögren C (September 2014). "The maintenance of chromosome structure: positioning and functioning of SMC complexes". Nature Reviews. Molecular Cell Biology. 15 (9): 601–14. doi:10.1038/nrm3857. PMID 25145851. S2CID 23908801.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ Potts PR, Yu H (July 2007). "The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins". Nature Structural & Molecular Biology. 14 (7): 581–90. doi:10.1038/nsmb1259. PMID 17589526. S2CID 7915836.
  14. ^ Grange LJ, Reynolds JJ, Ullah F, Isidor B, Shearer RF, Latypova X, et al. (November 2022). "Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy". Nature Communications. 13 (1): 6664. Bibcode:2022NatCo..13.6664G. doi:10.1038/s41467-022-34349-8. PMC 9636423. PMID 36333305.
  15. ^ Yan, Shunping; Wang, Wei; Marqués, Jorge; Mohan, Rajinikanth; Saleh, Abdelaty; Durrant, Wendy E.; Song, Junqi; Dong, Xinnian (2013-11-21). "Salicylic Acid Activates DNA Damage Responses to Potentiate Plant Immunity". Molecular Cell. 52 (4): 602–610. doi:10.1016/j.molcel.2013.09.019. ISSN 1097-2765. PMC 3863363. PMID 24207055.
  16. ^ 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.
  17. ^ 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.
  18. ^ Jiang, Jieming; Mao, Ning; Hu, Huan; Tang, Jiahang; Han, Danlu; Liu, Song; Wu, Qian; Liu, Yiyang; Peng, Changlian; Lai, Jianbin; Yan, Changwei (July 8, 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. 116 (30): 15288–15296. Bibcode:2019PNAS..11615288J. doi:10.1073/pnas.1900308116. ISSN 0027-8424. PMC 6660752. PMID 31285327.
  19. ^ Yu, You; Li, Shibai; Ser, Zheng; Kuang, Huihui; Than, Thane; Guan, Danying; Zhao, Xiaolan; Patel, Dinshaw J. (2022-06-07). "Cryo-EM structure of DNA-bound Smc5/6 reveals DNA clamping enabled by multi-subunit conformational changes". Proceedings of the National Academy of Sciences. 119 (23): e2202799119. Bibcode:2022PNAS..11902799Y. doi:10.1073/pnas.2202799119. ISSN 0027-8424. PMC 9191643. PMID 35648833.
  20. ^ Hong Y, Sonneville R, Agostinho A, Meier B, Wang B, Blow JJ, Gartner A (March 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.
  21. ^ Hwang G, Sun F, O'Brien M, Eppig JJ, Handel MA, Jordan PW (May 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.
  22. ^ van der Crabben SN, Hennus MP, McGregor GA, Ritter DI, Nagamani SC, Wells OS, et al. (August 2016). "Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease". The Journal of Clinical Investigation. 126 (8): 2881–92. doi:10.1172/JCI82890. PMC 4966312. PMID 27427983.

Further reading[edit]

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