Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.719821
Title: Molecular architecture of SAS-5 enables construction of a daughter centriole
Author: Rogala, Kacper Budzisław
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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Abstract:
In dividing cells, centrioles are duplicated once per cell cycle in a semi-conservative manner. A daughter centriole forms perpendicularly to the mother in a process templated by cartwheel-like structures. Cartwheels are found in centrioles of most eukaryotes, and are regarded as the key factor in establishing the nine-fold symmetry of centrioles. Cartwheels comprise the self-oligomerising protein SAS-6, recruitment of which to the mother centriole is mediated by direct binding to protein SAS-5 (also known as Ana2 or STIL). Although SAS-5 is an essential protein for centriole duplication, depletion of which completely terminates centrosome-dependent cell division, its exact role in this process has remained obscure. Using X-ray crystallography and a range of biophysical techniques, we have determined the molecular architecture of SAS-5. We show that SAS-5 forms a complex oligomeric structure, mediated by two self-associating domains: a trimeric coiled coil and a novel globular dimeric Implico domain. Disruption of either domain leads to centriole duplication failure in worm embryos, indicating that large SAS-5 assemblies are necessary for function. We propose that SAS-5 provides multivalent attachment sites that are critical for promoting assembly of SAS-6 into a cartwheel, and thus centriole formation.
Supervisor: Vakonakis, Ioannis ; Deane, Charlotte Sponsor: Engineering and Physical Sciences Research Council ; Boehringer Ingelheim Fonds ; Biotechnology and Biological Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.719821  DOI: Not available
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