SMC5

Last updated
SMC5
Identifiers
Aliases SMC5 , SMC5L1, structural maintenance of chromosomes 5
External IDs OMIM: 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 Mb Chr 19: 23.18 – 23.25 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

Contents

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

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

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. Smc5 6 complex with Nse proteins.png
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

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

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.

Related Research Articles

Heterochromatin is a tightly packed form of DNA or condensed DNA, which comes in multiple varieties. These varieties lie on a continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a role in the expression of genes. Because it is tightly packed, it was thought to be inaccessible to polymerases and therefore not transcribed; however, according to Volpe et al. (2002), and many other papers since, much of this DNA is in fact transcribed, but it is continuously turned over via RNA-induced transcriptional silencing (RITS). Recent studies with electron microscopy and OsO4 staining reveal that the dense packing is not due to the chromatin.

<i>Schizosaccharomyces pombe</i> Species of yeast

Schizosaccharomyces pombe, also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measure 3 to 4 micrometres in diameter and 7 to 14 micrometres in length. Its genome, which is approximately 14.1 million base pairs, is estimated to contain 4,970 protein-coding genes and at least 450 non-coding RNAs.

<span class="mw-page-title-main">Condensin</span>

Condensins are large protein complexes that play a central role in chromosome assembly and segregation during mitosis and meiosis. Their subunits were originally identified as major components of mitotic chromosomes assembled in Xenopus egg extracts.

<span class="mw-page-title-main">Spindle checkpoint</span> Cell cycle checkpoint

The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.

Subtelomeres are segments of DNA between telomeric caps and chromatin.

SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes.

The replication factor C, or RFC, is a five-subunit protein complex that is required for DNA replication.

<span class="mw-page-title-main">Cohesin</span> Protein complex that regulates the separation of sister chromatids during cell division

Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3. Cohesin holds sister chromatids together after DNA replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB.

<span class="mw-page-title-main">SMC1A</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 1A (SMC1A) is a protein that in humans is encoded by the SMC1A gene. SMC1A is a subunit of the cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells, cohesin is formed of SMC1A, SMC3, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3.

<span class="mw-page-title-main">RAD1 homolog</span> Protein-coding gene in the species Homo sapiens

Cell cycle checkpoint protein RAD1 is a protein that in humans is encoded by the RAD1 gene.

<span class="mw-page-title-main">RAD21</span> Protein-coding gene in the species Homo sapiens

Double-strand-break repair protein rad21 homolog is a protein that in humans is encoded by the RAD21 gene. RAD21, an essential gene, encodes a DNA double-strand break (DSB) repair protein that is evolutionarily conserved in all eukaryotes from budding yeast to humans. RAD21 protein is a structural component of the highly conserved cohesin complex consisting of RAD21, SMC1A, SMC3, and SCC3 [ STAG1 (SA1) and STAG2 (SA2) in multicellular organisms] proteins, involved in sister chromatid cohesion.

<span class="mw-page-title-main">SMC3</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 3 (SMC3) is a protein that in humans is encoded by the SMC3 gene. SMC3 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. In humans, SMC3 is present in all cohesin complexes whereas there are multiple paralogs for the other subunits.

<span class="mw-page-title-main">MUS81</span> Protein-coding gene in the species Homo sapiens

Crossover junction endonuclease MUS81 is an enzyme that in humans is encoded by the MUS81 gene.

<span class="mw-page-title-main">WAPAL</span> Protein-coding gene in the species Homo sapiens

Wings apart-like protein homolog (WAPL) is a protein that in humans is encoded by the WAPAL gene. WAPL is a key regulator of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. Cohesin has a ring-like arrangement and it is thought that it associates with the chromosome by entrapping it whether as a loop of DNA, a single strand or a pair of sister chromosomes. WAPL forms a complex with PDS5A or PDS5B and releases cohesin from DNA by opening the interface between SMC3 and RAD21.

<span class="mw-page-title-main">SMC4</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 4 (SMC-4) also known as chromosome-associated polypeptide C (CAP-C) or XCAP-C homolog is a protein that in humans is encoded by the SMC4 gene. SMC-4 is a core subunit of condensin I and II, large protein complexes involved in high order chromosome organization, including condensation and segregation. SMC-4 protein is commonly associated with the SMC-2 protein, another protein complex within the SMC protein family. SMC-4 dimerizes with SMC-2, creating the flexible and dynamic structure of the condensin holocomplex. An over-expression of the SMC-4 protein is shown to impact carcinogenesis.

<span class="mw-page-title-main">SMC6</span> 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.

<span class="mw-page-title-main">REC8</span> Protein-coding gene in the species Homo sapiens

Meiotic recombination protein REC8 homolog is a protein that in humans is encoded by the REC8 gene.

<span class="mw-page-title-main">SMC2</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 2 (SMC-2), also known as chromosome-associated protein E (CAP-E), is a protein that in humans is encoded by the SMC2 gene. SMC2 is part of the SMC protein family and is a core subunit of condensin I and II, large protein complexes involved in chromosome condensation, overall organization. Several studies have demonstrated the necessity of SMC2 for cell division and proliferation.

Sister chromatid cohesion refers to the process by which sister chromatids are paired and held together during certain phases of the cell cycle. Establishment of sister chromatid cohesion is the process by which chromatin-associated cohesin protein becomes competent to physically bind together the sister chromatids. In general, cohesion is established during S phase as DNA is replicated, and is lost when chromosomes segregate during mitosis and meiosis. Some studies have suggested that cohesion aids in aligning the kinetochores during mitosis by forcing the kinetochores to face opposite cell poles.

<span class="mw-page-title-main">SMC1B</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 1B (SMC-1B) is a protein that in humans is encoded by the SMC1B gene. SMC proteins engage in chromosome organization and can be broken into 3 groups based on function which are cohesins, condensins, and DNA repair.SMC-1B belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis. SMC1ß protein appears to participate with other cohesins REC8, STAG3 and SMC3 in sister-chromatid cohesion throughout the whole meiotic process in human oocytes.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000198887 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 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.
  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.
  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. 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. 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.

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