Biology:SMC5

From HandWiki

Structural maintenance of chromosomes protein 5 is a protein encoded by the SMC5 gene in human.[1][2] 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.[3] 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.[3] 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.[4][5] 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. [6][7][8]

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


It is involved in the Alternative lengthening of telomeres cancer mechanism.[9]

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.[10] The SMC-5/6 complex in mouse oocytes is essential for the formation of segregation competent bivalents during meiosis.[11] 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.[12] Patient's cells display chromosome rearrangements, micronuclei, sensitivity to DNA damage and defective homologous recombination.

References

  1. ↑ "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. February 1998. doi:10.1093/dnares/5.1.31. PMID 9628581. 
  2. ↑ "Entrez Gene: SMC5 structural maintenance of chromosomes 5". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23137. 
  3. ↑ 3.0 3.1 "The maintenance of chromosome structure: positioning and functioning of SMC complexes". Nature Reviews. Molecular Cell Biology 15 (9): 601–14. September 2014. doi:10.1038/nrm3857. PMID 25145851. 
  4. ↑ "A novel SMC protein complex in Schizosaccharomyces pombe contains the Rad18 DNA repair protein". The EMBO Journal 19 (7): 1691–702. April 2000. doi:10.1093/emboj/19.7.1691. PMID 10747036. 
  5. ↑ "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. December 1995. doi:10.1128/mcb.15.12.7067. PMID 8524274. 
  6. ↑ "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. December 2006. doi:10.1074/jbc.M608004200. PMID 17005570. 
  7. ↑ "Chromatin association of the SMC5/6 complex is dependent on binding of its NSE3 subunit to DNA". Nucleic Acids Research 44 (3): 1064–1079. February 2016. doi:10.1093/nar/gkv1021. PMID 26446992. 
  8. ↑ "A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6". Scientific Reports 10 (1): 9694. June 2020. doi:10.1038/s41598-020-66647-w. PMID 32546830. Bibcode: 2020NatSR..10.9694V. 
  9. ↑ "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. July 2007. doi:10.1038/nsmb1259. PMID 17589526. 
  10. ↑ "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. March 2016. doi:10.1371/journal.pgen.1005872. PMID 27010650. 
  11. ↑ "SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes". Development 144 (9): 1648–1660. May 2017. doi:10.1242/dev.145607. PMID 28302748. 
  12. ↑ "Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease". The Journal of Clinical Investigation 126 (8): 2881–92. August 2016. doi:10.1172/JCI82890. PMID 27427983. 

Further reading





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