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F r o m W i k i p e d i a , t h e f r e e e n c y c l o p e d i a
Protein-coding gene in the species Homo sapiens
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 discoveries are shedding light on the various functions.[7] The SMC complex mediates long-distance interactions that enable higher-order chromatin folding in interphase. The SMC complex has an ATPase activity, a conserved kleisin, and 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 ]
^ "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 .
^ 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 .
^ "Entrez Gene: SMC5 structural maintenance of chromosomes 5" .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 ]
Taylor EM, Moghraby JS, Lees JH, Smit B, Moens PB, Lehmann AR (June 2001). "Characterization of a novel human SMC heterodimer homologous to the Schizosaccharomyces pombe Rad18/Spr18 complex" . Molecular Biology of the Cell . 12 (6 ): 1583–94. doi :10.1091/mbc.12.6.1583 . PMC 37326 . PMID 11408570 .
Potts PR, Yu H (August 2005). "Human MMS21/NSE2 is a SUMO ligase required for DNA repair" . Molecular and Cellular Biology . 25 (16 ): 7021–32. doi :10.1128/MCB.25.16.7021-7032.2005 . PMC 1190242 . PMID 16055714 .
Potts PR, Porteus MH, Yu H (July 2006). "Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks" . The EMBO Journal . 25 (14 ): 3377–88. doi :10.1038/sj.emboj.7601218 . PMC 1523187 . PMID 16810316 .
R e t r i e v e d f r o m " https://en.wikipedia.org/w/index.php?title=SMC5&oldid=1222869324 "
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