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Title: Structural and biochemical studies of cohesin regulation by Wpl1
Author: Chatterjee, A.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Sister chromatid cohesion physically tethers the sister chromatids formed after DNA replication ensuring biorientation and proper segregation of chromosomes. Cohesion is mediated by a ring shaped protein complex called cohesin, formed of the conserved subunits – Smc1, Smc3, Scc1 and Scc3 (in yeast). Additionally, several regulatory proteins control the cohesin complex, important among which are Eco1 and Wpl1. These two proteins have been shown to have opposing functions, wherein Wpl1 tends to maintain cohesin in a noncohesive state whereas Eco1 counteracts this effect by acetylating cohesin, which switches the complex to a cohesive state. Nevertheless, the detailed mechanism of functioning of these proteins and as a result, the process of cohesion establishment and regulation as a whole still remains poorly understood. The present work describes characterization of the protein Wpl1 using structurefunction studies in order to understand the process of cohesin regulation in further detail. The conserved domain of Wpl1, called WAPL, was found to directly interact with the ATPase head of the Smc3 subunit of the cohesin complex. The interaction has been verified using various biophysical and biochemical methods. In addition, crystal structures of the WAPL domain alone and in complex with an interacting stretch of the Smc3 have been described. Together with the complementary functional studies, the structures reveal novel features and probable mechanism by which Wpl1 may regulate sister chromatid cohesion. Thus, the work has provided mechanistic insights into the functioning of the protein and an improvement in the understanding of regulation of cohesion.
Supervisor: Singleton, M. R. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available