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The handle http://hdl.handle.net/1887/43800 holds various files of this Leiden University dissertation.

Author: Helfricht, A.

Title: Chromatin modifiers in DNA repair and human disease Issue Date: 2016-11-01

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Chromatin modifiers in DNA repair and human disease

Angela Helfricht

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Cover design & layout: Angela Helfricht

Printing: Off Page, Amsterdam, the Netherlands www.offpage.nl

ISBN: 978-94-6182-719-7

© Copyright 2016 by Angela Helfricht

All rights reserved. No parts of this thesis may be reprinted, reproduced or utilised in any form or by electronic, mechanical, or other means, now known or hereafter devised, includ- ing photocopying and recording in any information storage or retrieval system without the expressed, written consent of the author.

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Chromatin modifiers in DNA repair and human disease

Proefschrift

ter verkrijging van de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus Prof.mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op dinsdag 1 november 2016

klokke 13:45 uur

door

Angela Helfricht

geboren te Dresden, Duitsland in 1984

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Promotor: Prof.dr.ir. S. M. van der Maarel Co-promotoren: Dr. H. van Attikum

Dr. A.C.O. Vertegaal

Leden promotiecommissie: Prof.dr. M. Tijsterman

Prof.dr. R. Kanaar (Erasmus MC) Dr. M. v. d. Burg (Erasmus MC)

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Willst du dich am Ganzen erquicken, so musst du das Ganze im Kleinsten erblicken.

Johan Wolfgang von Goethe (1827)

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TABLE OF CONTENTS CHAPTER 1

General introduction 10

Aim of this study 37

CHAPTER 2

Identification of EHMT1 as a chromatin factor that negatively regulates 53BP1 accrual during the DNA double-strand break

response 52

CHAPTER 3

Remodeling and spacing factor 1 (RSF1) deposits centromere proteins at DNA double-strand breaks to promote non-

homologous end-joining 80

CHAPTER 4

Investigating DNA damage-induced RSF1 SUMOylation 108

CHAPTER 5

Loss of ZBTB24, a novel non-homologous end-joining protein,

impairs class-switch recombination in ICF syndrome 126 CHAPTER 6

Perspectives 168

CHAPTER 7

Appendix: English summary 182 Nederlandse samenvatting 184 Deutsche Zusammenfassung 186

Curriculum vitae 188

List of publications 189

Acknowledgements 190

Referenties

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