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Title: The role of the Smc5/6 complex in meiosis
Author: Newcombe, Sonya
ISNI:       0000 0004 6348 4356
Awarding Body: University of Sussex
Current Institution: University of Sussex
Date of Award: 2017
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Meiosis is a specialised cell division that results in the production of haploid gametes. Errors in meiotic chromosome transmission can lead to chromosomally imbalanced embryos which lead to miscarriage or if the offspring survive to term congenital birth defects. SMC proteins are well known to have roles in regulating chromosome segregation, condensation and repair. The roles of cohesin and condensin in chromosome cohesion and condensation are well characterised. Much less is known about the third SMC complex, the Smc5/6 complex. The Smc5/6 complex is known to have roles in both DNA repair and cohesin regulation during mitosis. The work outlined here demonstrates that the Smc5/6 complex also has important roles in both Saccharomyces cerevisiae and mouse female meiosis. Live cell imaging in Saccharomyces cerevisiae demonstrated that the Smc5/6 complex is required for meiotic chromosome segregation and cohesin regulation. To investigate if the Smc5/6 complex also played a similar role in mammalian meiosis, oocytes from Smc6GT/+ mice were analysed. Smc6GT/GT mice are embryonic lethal. Contrastingly Smc6GT/+ mice are relatively unaffected. The only phenotype observed in Smc6GT/+ mice was reduced litter sizes. Interestingly analysis of the lost embryos, from Smc6GT/+ mouse crosses, found that they were not lost because they were homozygous for Smc6GT/GT. The lost embryos were either wild type or Smc6GT/+ (Ju et al, 2013). The work outlined here indicates it is likely that the embryos were lost due to aneuploidy in the oocytes from the Smc6GT/+ mother. Many of the metaphase II oocytes from the Smc6GT/+ mother were found to be aneuploid. Subsequent analysis of metaphase I oocytes from the Smc6GT/+ mother indicated that the aneuploidy was due to weakened cohesion, as demonstrated by the increased numbers of separated homologous chromosomes in the MI oocytes from the Smc6GT/+ mother and the overall reduced levels of acetylated Smc3 staining. It was also observed that chromosome condensation was affected in the oocytes from the Smc6GT/+ mother. This indicates that the Smc5/6 complex plays an important role in promoting accurate chromosome segregation in mammalian meiosis alongside both cohesin and condensin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH0605.3 Meiosis