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Structural characterisation of proteins at the cohesion/replication interface

Hodáková, Zuzana; (2021) Structural characterisation of proteins at the cohesion/replication interface. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Cohesion establishment and DNA synthesis are tightly regulated processes occurring at the replication fork. DNA synthesis is under the control of the replisome; a complex machinery of numerous proteins which mediate DNA unwinding and DNA synthesis. Factors interacting with the replisome facilitate replication-related events ahead and behind the fork. Arising impediments ahead of the replisome are resolved by specialised helicases and DNA repair complexes. Conversely, events occurring behind the fork focus not only on DNA synthesis but also on the joining of the newly synthesised sister chromatids. The protein complex cohesin is responsible for ensuring that the sisters are joined immediately after replication and remain held together until anaphase. The precise spatiotemporal relations of proteins at the replication fork have not been fully elucidated. This thesis addresses two important questions of cohesion establishment using structural biology tools. The first focuses on a long outstanding question on the mechanisms of cohesin loading onto DNA. It exposes insights into the folding mechanism of cohesin upon loading, governed by its accessory complex, the cohesin loader. The thesis further describes the variety of modifications which can be applied to study cohesin, and characterises the overall architectures of the loader complexes. The second question studied in this thesis describes the link between cohesion and DNA replication via the small helicase Chl1. There is currently no structure of Chl1 available and therefore the presented Chl1 envelope is the first structural characterisation of this helicase, pointing to a conserved architecture amongst the XPD subfamily of helicases. Additional work focuses on studying a potential auto-inhibition mechanism contributing to the function of this helicase in response to replication stress.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Structural characterisation of proteins at the cohesion/replication interface
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10125316
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