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 homozygousmutant 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
↑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. PMID12747765.
↑ 6.06.16.2Gerdin 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.
↑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. PMID16541025.
↑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. PMID19965387.
↑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. PMID24055156.
Wang X, Dai W (Oct 2005). "Shugoshin, a guardian for sister chromatid segregation". Experimental Cell Research. 310 (1): 1–9. doi:10.1016/j.yexcr.2005.07.018. PMID16112668.
Fu G, Ding X, Yuan K, Aikhionbare F, Yao J, Cai X, Jiang K, Yao X (Jul 2007). "Phosphorylation of human Sgo1 by NEK2A is essential for chromosome congression in mitosis". Cell Research. 17 (7): 608–18. doi:10.1038/cr.2007.55. PMID17621308.
Pouwels J, Kukkonen AM, Lan W, Daum JR, Gorbsky GJ, Stukenberg T, Kallio MJ (Jul 2007). "Shugoshin 1 plays a central role in kinetochore assembly and is required for kinetochore targeting of Plk1". Cell Cycle. 6 (13): 1579–85. doi:10.4161/cc.6.13.4442. PMID17617734.
Fu G, Hua S, Ward T, Ding X, Yang Y, Guo Z, Yao X (Jun 2007). "D-box is required for the degradation of human Shugoshin and chromosome alignment". Biochemical and Biophysical Research Communications. 357 (3): 672–8. doi:10.1016/j.bbrc.2007.03.204. PMID17448445.
Yang Y, Wang X, Dai W (Apr 2006). "Human Sgo1 is an excellent target for induction of apoptosis of transformed cells". Cell Cycle. 5 (8): 896–901. doi:10.4161/cc.5.8.2691. PMID16628005.
Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H (May 2006). "PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation". Developmental Cell. 10 (5): 575–85. doi:10.1016/j.devcel.2006.03.010. PMID16580887.
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. PMID16541025.
Kitajima TS, Hauf S, Ohsugi M, Yamamoto T, Watanabe Y (Feb 2005). "Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization". Current Biology. 15 (4): 353–9. doi:10.1016/j.cub.2004.12.044. PMID15723797.