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Title: An investigation into crosstalk between cohesion and the Smc5/6 complex during the cell cycle
Author: Mykura, Charlotte
ISNI:       0000 0004 7229 4431
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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Elaborate mechanisms have evolved which allow cells to faithfully segregate their DNA into two daughters during each cell cycle. Such mechanisms ensure that DNA is stably inherited over generations, and also is a dynamic, functional entity in the context of the cell cycle. A set of protein complexes which are key players in governing chromatin architecture during the cell cycle are the Structural Maintenance of Chromosomes (SMC) complexes; cohesin, the Smc5/6 complex and condensin. Cohesin is essential for sister chromatids to remain associated from their synthesis in S-phase right up until they are separated during mitosis. This cohesion is thought to be mediated by the ability of cohesin to physically embrace DNA strands within its ring-like structure. For cohesin to form cohesive links between sister chromatids, it must first be acetylated by the Eco1 acetyl transferase, and following cohesion generation in S-phase, Eco1 is degraded. During mitosis, it is essential that cohesion be removed to prevent aberrant mitoses. Cohesin maintains sister chromatid identity, but also facilitates homologous recombination should DNA damage occur. Our knowledge of the Smc5/6 complex thus far heavily implicates it in DNA damage repair. However, growing evidence suggests that the Smc5/6 complex and cohesion dynamics could be mechanistically linked. This investigation submits evidence exploring the hypothesis that the Smc5/6 complex may be regulating cohesion during an unperturbed cell cycle. A study of a putative interaction between Smc5/6 and Mck1 leads us to propose that the Smc5/6 complex has a role, directly or indirectly in Eco1 turnover. Further, evidence presented suggests that the Smc5/6 complex may have a role in regulating cohesin acetylation by Eco1. This investigation also involves the study of an Eco1 putative SUMO interacting motif.
Supervisor: Aragon, Luis Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral