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 41
component of the SUMO-2/3 cycle Chapter 3 USP11 Counteracts RNF4 and Stabilizes 63
PML Nuclear Bodies Chapter 4 Site-Specific Identification of SUMO-2 Targets 87
in Cells Reveals an Inverted SUMOylation Motif and a Hydrophobic Cluster SUMOylation Motif Chapter 5 Uncovering SUMOylation Dynamics During Cell 117
Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein Chapter 6 The Cockayne Syndrome-B protein is SUMOylated 155
upon UV induced DNA damage Chapter 7: Summary and discussion 181 Chapter 8: Nederlandse samenvatting 195
List of abbreviations 201
Curriculum Vitae 207
List of publications 209
