SGOL1

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
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RefSeq (mRNA)

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RefSeq (protein)

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Shugoshin-like 1 is a protein that in humans is encoded by the SGOL1 gene.[1][2]

Model organisms

Model organisms have been used in the study of SGOL1 function. A conditional knockout mouse line, called Sgol1tm1a(EUCOMM)Wtsi[8][9] has been generated.[10][11][12]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[6][13] Twenty six tests were carried out on mutant mice and three significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and thus none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and a decreased regulatory T cell number was observed in male animals.[6]

Mechanisms

A physical mechanism that guarantees the accurate segregation of sister chromatids during mitosis arises from the ring shaped cohesin complex consisting of 4 subunits (SMC1A/B, SMC3, SCC1, and SA1/2 in humans). This complex encircles the two sister chromatids and resists the pulling force of microtubules.[14] The characteristic X-shape chromosomes are formed due to the centromeric cohesin protected by Shugoshin-PP2A complex.[15]

Kinetochore localization of Sgo1-PP2A is dependent upon phosphorylation on histone H2A of nucleosome, which is the important substrate of spindle checkpoint kinase BUB1.[16] Centromeric cohesin and H2A-pT120 specify two distinct pools of Sgo1-PP2A at inner centromeres and kinetochores respectively,[17] while the CDK1/cyclin B phosphorylation on Sgo1 is essential for Sgo1-PP2A to protect centromeric cohesin, not only for bringing PP2A to cohesin,[18] but also physically shield out the negative regulator WAPAL from cohesin.[19]

References

  1. Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO, Jäger D, Chen YT, Mackay A, O'Hare MJ, Old LJ (Mar 2001). "Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression". Cancer Immunity. 1: 4. PMID 12747765.
  2. "Entrez Gene: SGOL1 shugoshin-like 1 (S. pombe)".
  3. "Peripheral blood lymphocytes data for Sgol1". Wellcome Trust Sanger Institute.
  4. "Salmonella infection data for Sgol1". Wellcome Trust Sanger Institute.
  5. "Citrobacter infection data for Sgol1". Wellcome Trust Sanger Institute.
  6. 6.0 6.1 6.2 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  7. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  8. "International Knockout Mouse Consortium".
  9. "Mouse Genome Informatics".
  10. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  11. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  12. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  13. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  14. Nasmyth K, Haering CH. "Cohesin: its roles and mechanisms". Annual Review of Genetics. 43: 525–58. doi:10.1146/annurev-genet-102108-134233. PMID 19886810.
  15. Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y (May 2006). "Shugoshin collaborates with protein phosphatase 2A to protect cohesin". Nature. 441 (7089): 46–52. doi:10.1038/nature04663. PMID 16541025.
  16. Kawashima SA, Yamagishi Y, Honda T, Ishiguro K, Watanabe Y (Jan 2010). "Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin". Science. 327 (5962): 172–7. doi:10.1126/science.1180189. PMID 19965387.
  17. Liu H, Jia L, Yu H (Oct 2013). "Phospho-H2A and cohesin specify distinct tension-regulated Sgo1 pools at kinetochores and inner centromeres". Current Biology. 23 (19): 1927–33. doi:10.1016/j.cub.2013.07.078. PMID 24055156.
  18. Liu H, Rankin S, Yu H (Jan 2013). "Phosphorylation-enabled binding of SGO1-PP2A to cohesin protects sororin and centromeric cohesion during mitosis". Nature Cell Biology. 15 (1): 40–9. doi:10.1038/ncb2637. PMC 3531828. PMID 23242214.
  19. Hara K, Zheng G, Qu Q, Liu H, Ouyang Z, Chen Z, Tomchick DR, Yu H (Oct 2014). "Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion". Nature Structural & Molecular Biology. 21 (10): 864–70. doi:10.1038/nsmb.2880. PMC 4190070. PMID 25173175.

Further reading