Changes in chromatin organization of human cells in response to genotoxic stress
Abdel-Halim Mahfouz, H.I.
Citation
Abdel-Halim Mahfouz, H. I. (2009, February 24). Changes in chromatin organization of human cells in response to genotoxic stress. Retrieved from https://hdl.handle.net/1887/13517
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Changes in chromatin organization of human cells in response to genotoxic stress
Howyda Ibrahim Abdel-Halim Mahfouz
Changes in chromatin organization of human cells in response to genotoxic stress
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus Prof. mr. P.F. van der Heijden, volgens besluit van het College voor Promoties
te verdedigen op dinsdag 24 februari 2009 klokke 13.45 uur
door
Howyda Ibrahim Abdel-Halim Mahfouz Geboren te Ismailia, Egypte
in 1969
Promotiecommissie
Promotor: Prof. Dr. L.H.F. Mullenders
Referent: Dr. P. de Boer (UMCN)
Overige leden: Prof. Dr. A. K. Raap
Prof. Dr. D. G. de Rooij (UU)
Changes in chromatin organization of human cells in response to genotoxic stress
ISBN: 9789071382901
Printed by Gildeprint Drukkerijen B.V., Enschede
The research described in this thesis was performed in the Department of Toxicogenetics, Leiden University Medical Center (LUMC), The Netherlands.
Part of this thesis was financially supported by a fellowship from the Egyptian government to the author.
Cover: Microscopic images describing chromosome-9 homologues in human cells exposed to mitomycin C.
“There is no gene for human spirit or fate”
from the film GATTACA
Dedicated To my parents
Contents
Aim and Outline of the Thesis 9
Chapter 1 DNA damage, cellular stress response, and changes in chromatin organization
15
1.1 Introduction 17
1.2 Different types of cellular stress 18
1.2.1 Ionizing radiation 19
1.2.2 Ultraviolet radiation 19
1.2.3 Cross-linking agents 20
1.2.4 Heat shock 21
1.3 Cellular responses to DNA damage 24
1.3.1 DNA repair 25
NER 26
DSB repair (NHEJ and HR) 28
ICL repair 32
1.3.2 Transcription response 34
1.4 Chromosome organization of interphase nuclei 35 1.4.1 Pairing of homologous chromosomes 38 1.4.2 Heterochromatin: structure and function 40 1.4.3 Changes, repositioning and pairing of chromatin
after DNA damage
43
Chapter 2 Mitomycin C-induced pairing of heterochromatin reflects initiation of DNA repair and chromatid exchange formation (Abdel-Halim et al., 2005, J. Cell Science 118, 1757-1767)
65
Chapter 3 Ionizing radiation-induced instant pairing of heterochromatin of homologous chromosomes in human cells (Abdel-Halim et al., 2004, Cytogenet.
Genome Res. 104, 193-199)
79
Chapter 4 Pairing of heterochromatin in response to cellular stress (Abdel-Halim et al., 2006, Exp. Cell Res. 312, 1961-1969)
89
Chapter 5 Impact of DNA repair on the DNA damage-induced heterochromatin pairing in human cells (In preparation)
101
Summary and Discussion 123
Dutch summary 135
Arabic summary 141
Abbreviations 145
List of publications 147
Curriculum vitae 149
