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Title: Investigation into the role of the SMC5/6 complex in human cells
Author: McGregor, Grant Alexander
ISNI:       0000 0004 6350 1291
Awarding Body: University of Sussex
Current Institution: University of Sussex
Date of Award: 2017
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The Structural Maintenance of Chromosome (SMC) family of proteins are required to regulate almost all aspects of chromosome biology and are critical for genomic stability. The SMC5/6 complex, a member of this family, is composed of two SMC heterodimers and six additional Non-SMC Elements 1-6. The components of SMC5/6 possess activities including ATPases, ubiquitin and SUMO ligases. SMC5/6 is required in homologous recombination and for accurate chromosome segregation. Loss of SMC5/6 is lethal in yeasts, embryonic lethal in mice and mutations in NSMCE2 leads to primordial dwarfism and insulin resistance. This thesis focuses on a mutation in NSMCE3, found in American and Dutch families, that results in a novel chromosomal breakage syndrome characterized by fatal pulmonary disease. Another focus is the development, execution and validation of a microscopy based synthetic sick/lethal screen using cells with knockdown of NSMCE4a. Studies of SMC5/6 in yeasts predict that compromising SMC5/6 function would lead to a dependence on other DNA repair pathways. The results combined with patient data confirm that SMC5/6 is important in the absence of repair by non-homologous end joining and is particularly important under conditions of replication stress.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD0415 Biochemistry