Cover Page The handle http://hdl.handle.net/1887/28538 holds various files of this Leiden University dissertation Author: Schimmel, Joost Title: Regulation of genome stability and cell cycle progression by SUMOylation Issue Date: 2014-09-09 Regulation of genome stability and cell cycle progression by SUMOylation Joost Schimmel Copyright © 2014 by J. Schimmel. All rights reserved. Copyright of the individual chapters rests with the authors with te following exceptions: Chapter 1: John Wiley & Sons, Inc Chapter 2: the American Society for Biochemistry and Molecular Biology Chapter 4 and 5: Elsevier - Cell Press (Molecular Cell) Regulation of genome stability and cell cycle progression by SUMOylation 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 9 september 2014 klokke 13.45 uur door Joost Schimmel geboren te Lopik op 17 april 1984 Promotiecommissie: Promotor: Prof. dr. P. ten Dijke Copromotor: Dr. A.C.O Vertegaal Overige leden: Prof. dr. T.K.Sixma (NKI, Amsterdam) Prof. dr. G.J.P.L. Kops (UMC, Utrecht) Dr. P. Knipscheer (Hubrecht Instituut, Utrecht) The studies described in this thesis were performed at the department of Molecular and Cellular Biology, Leiden University Medical Center and was financed by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO). Cover: Painting by Hiroyuki Kimura. Photographed by Naosuke ii With kind permission of both artist and photographer. Printed by: Proefschriftmaken.nl || Uitgeverij BOXPress Published by: Uitgeverij BOXPress, 's-Hertogenbosch ISBN:978-90-8891-919-0 The printing of this thesis was financially supported by the J.E. Jurriaanse Stichting and Greiner Bio-One. "I was just guessing at numbers and figures, pulling the puzzles apart. Questions of science, science and progress do not speak as loud as my heart." - Coldplay, The Scientist - aan mijn familie voor Karin Table of contents Aim and outline of the thesis 9 Chapter 1 Introduction 13 Chapter 2 The ubiquitin-proteasome system is a key component of the SUMO-2/3 cycle 41 Chapter 3 USP11 Counteracts RNF4 and Stabilizes PML Nuclear Bodies 63 Chapter 4 Site-Specific Identification of SUMO-2 Targets in Cells Reveals an Inverted SUMOylation Motif and a Hydrophobic Cluster SUMOylation Motif 87 Chapter 5 Uncovering SUMOylation Dynamics During Cell Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein 117 Chapter 6 The Cockayne Syndrome-B protein is SUMOylated upon UV induced DNA damage 155 Chapter 7: Summary and discussion181 Chapter 8: Nederlandse samenvatting 195 List of abbreviations 201 Curriculum Vitae 207 List of publications 209