University of Groningen Interactions between DNA damage and metabolism Huerta Guevara, Ana

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University of Groningen

Interactions between DNA damage and metabolism

Huerta Guevara, Ana

DOI:

10.33612/diss.123699652

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Publication date: 2020

Link to publication in University of Groningen/UMCG research database

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Huerta Guevara, A. (2020). Interactions between DNA damage and metabolism. University of Groningen. https://doi.org/10.33612/diss.123699652

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Interactions between DNA damage

and metabolism

by

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The research described in this thesis was primarily conducted at the Department of Pediatrics, Section Molecular Metabolism and Nutrition, University Medical Center Groningen, The Netherlands. This project received funding from the Mexican National Council of Science and Technology (CONACyT), and the Jan Kornelis de Cock stichting. Printing of this thesis was financially supported by the University of Groningen, the University Medical Center Groningen, the Graduate School of Medical Sciences, research Institute for Drug Exploration (GUIDE) and University of Groningen Library.

Huerta Guevara, Ana Patricia

Interactions between DNA damage and metabolism PhD dissertation, University of Groningen, The Netherlands

Cover design: Ana Huerta, ProefschriftMaken.nl Cover image: Suruchi Nepal, Laura Pérez-Vera Layout: ProefschriftMaken.nl

Printed by: ProefschriftMaken.nl

ISBN (printed): 978-94-034-2577-1 ISBN (digital): 978-94-034-2576-4

All rights reserved. No part of this publication may be reproduced, distributed, stored in retrieval system or transmitted, in any form or by any means, without permission of the author and the publisher holding respective copyrights of the published articles, if applicable.

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Interactions between DNA damage

and metabolism

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on

Wednesday 6 May 2020 at 12.45 hours by

Ana Patricia Huerta Guevara born on 9 May 1988 in Huamantla, Mexico

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Supervisor Prof. J.W. Jonker Co-supervisor Dr. J.K. Kruit Assessment Committee Prof. R. Shiri-Sverdlov Prof. M.A.T.M. van Vugt Prof. C. F. Calkhoven

Supervisor

Prof. J.W. Jonker

Co-supervisor

Dr. J.K. Kruit

Assessment Committee

Prof. R. Shiri-Sverdlov Prof. M.A.T.M. van Vugt Prof. C. F. Calkhoven

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Paranymphs

Suruchi Nepal Jonathan J. Bakker

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Table of contents

CHAPTER 1 General Introduction

CHAPTER 2 Increased insulin sensitivity and diminished pancreatic beta-cell function in DNA repair deficient Ercc1d/-_mice

CHAPTER 3 Failure to repair endogenous DNA damage in beta-cells causes adult onset diabetes

CHAPTER 4 Partial deficiency in Ercc1 expression in beta-cells is associated with impairments in glucose metabolism

CHAPTER 5 Mice with a hepatocyte-specific deletion of nuclear receptor TR4 (Nr2c2) display normal glucose homeostasis and a mild high-fat diet-induced dyslipidemia

CHAPTER 6 General Discussion and perspective Appendices 11 35 55 87 109 137 153