Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.797282
Title: Regulation and substrate specificity of the USP1-UAF1 deubiquitinase complex
Author: Arkinson, Connor
ISNI:       0000 0004 8503 2828
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2020
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Abstract:
Ubiquitination regulates numerous cellular signalling pathways in eukaryotes, such as DNA replication, cell cycle control and protein turnover. Ubiquitination is a reversible post-translational modification involving the assembly and removal of ubiquitin proteins. A superfamily of proteases known as the deubiquitinases (DUBs) target ubiquitin and remove it from substrates. As well as modifying thousands of target protein sites, ubiquitin is also conjugated to other ubiquitins at various sites, forming ubiquitin chains. This results in an enormous range of structurally diverse ubiquitin signals that a relatively small array of DUBs are required to regulate. The USP1 DUB, along with its activating binding partner UAF1, regulates a structurally diverse array of site-specifically monoubiquitinated substrates including PCNA-K164Ub, FANCD2-K561Ub and FANCI-K523Ub. Loss of USP1-UAF1 activity results in genomic instability, but how USP1 targets its substrates or is regulated by UAF1 is poorly understood. For example, how does a deubiquitinase (e.g. USP1) display high promiscuity yet target specific substrates? In this thesis, the minimal requirements for deubiquitination of FANCD2-K561Ub, FANCI-K523Ub and PCNA-K164Ub (USP1 physiological substrates) are determined by reconstitution and dissection of USP1. This thesis presents new insights into how DUBs achieve specific deubiquitination of ubiquitin-substrate conjugates and provides a molecular rationale for USP1 as the DUB for FANCD2-Ub.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.797282  DOI: Not available
Keywords: QR Microbiology
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