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University of Groningen The impact of genotoxic stress on protein homeostasis Huiting, Wouter

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University of Groningen

The impact of genotoxic stress on protein homeostasis

Huiting, Wouter

DOI:

10.33612/diss.168249330

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2021

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Huiting, W. (2021). The impact of genotoxic stress on protein homeostasis: a study on an emerging theme and its relevance for age-related degeneration. University of Groningen.

https://doi.org/10.33612/diss.168249330

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the

impact

of

genotoxic stress

A study on an emerging theme

and its relevance for

age-related degeneration

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The research described in this thesis was conducted at the University of Groningen, University Medical Center Groningen, The Netherlands, at the Department of Biomedical Sciences of Cells and Systems, and within the European Research Institute for the Biology of Ageing (ERIBA), between 2016 and 2021. The research was financially supported by the Netherlands Organisation for Scientific Research (NWO). Printing of this thesis was financially supported by the University of Groningen.

Cover Design: Sita Dijkstra, @zonniger INSTAGRAM Thesis Layout: Els Kuiper, www.elskuiper.nl Thesis printed by: Gildeprint, www.gildeprint.nl

Copyright © 2021 by Wouter Huiting. All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without permission of the author.

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The impact of genotoxic stress on

protein homeostasis

A study on an emerging theme and its relevance for age-related degeneration

Proefschrift

ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen

op gezag van de

rector magnificus prof. dr. C. Wijmenga en volgens besluit van het College voor Promoties

De openbare verdediging zal plaatsvinden op Maandag 10 mei 2021 om 11.00 uur

door

Wouter Huiting

Geboren op 10 juni 1990 te Nieuwegein

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SUPERVISORS

Dr. Steven Bergink

Prof. dr. Harm H. Kampinga

ASSESSMENT COMMITTEE

Prof. dr. Ineke Braakman

Prof. dr. Zuzana Storchová Prof. dr. Marcel van Vugt

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PARANYMPHS

Suzanne Dekker Els Kuiper

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Chapter 1

Introduction

9

Chapter 2

Impaired function of ATM, ATR, and DNA topoisomerases triggers the aggregation of a metastable subproteome through an overload of protein quality control systems

43

Chapter 3

Differential extraction of detergent-insoluble protein aggregates from cultured mammalian cells - a benchtop centrifuge method

79

Chapter 4

Loss of protein homeostasis is a common pathological mechanism in DNA damage response-compromised Caenorhabditis elegans

93 Chapter 5 Discussion 115 Bibliography 131 Appendix

List of abbreviations used English summary

Nederlandse samenvatting Acknowledgements

Short CV with a list of publications

167 171 177 183 191

CONTENTS

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