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Promotiecommissie Promotoren: Prof. dr. J.H.J. Hoeijmakers Prof. dr. D. Bootsma Overige leden: Prof. dr. F.G. Grosveld Prof. dr. J.A. Grootegoed Dr. F.R. de Gruijl Co-promotor: Dr. G. Weeda Omslag: George, 1998 Dit proefschrift kwam tot stand binnen de vakgroep Celbiologie en Genetilea van de Faculteit der Geneeskunde en Gezondbeidswetenschappen aan de Erasmus Universiteit Rotterdam. De vakgroep maakt deel uit van het Medisch Genetisch Centrum Zuid-West Nederland. Het onderzoek en de publikatie van dit proefschrift zijn financieel ondersteund door het Koningin Wilhelmina Fonds, Johnson&Johnson, New Brunswick, USA en Elektromotoren Bracke RV., Clinge.
CONTENTS Aim of the thesis 5 Chapter 1 Nucleotide excision repair and human syndromes 7 Chapter 2 Mouse models to study the consequences of defective nucleotide 27 eXCISIOn reparr. Biochimie, in press Chapter 3 Disruption of the mouse xeroderma pigmentosum group D DNA 47 repairlbasal transcription gene results in preimplantation lethality. Cancer Res. 58:89-94 (1998) Chapter 4 A mouse model for the basal transcription/DNA repair syndrome 63 trichothiodystrophy. Mol. Cell f: 98 f -990 (1998) Chapter 5 Mouse model for the DNA repairlbasal transcription disorder 85 trichothiodystrophy reveals cancer predisposition Submitted for publication Chapter 6 Symptoms of premature ageing in a mouse model for the DNA 103 repair Ibasal transcription syndrome trichothiodystrophy Manuscript in prep. Sununary and conclusion 121 Samenvatting voor niet-biologen 127 Curriculum vitae l31 Publications l32 Dankwoord 134
Page 1: A MOUSE MODEL FOR TRICHOTHIODYSTROP
Page 5: AIM OF THE THESIS Nucleotide excisi
Page 9 and 10: NUCLEOTIDE EXCISION REPAIR AND HUMA
Page 11 and 12: capacity to generate bulky base add
Page 14 and 15: strong interaction between XPG and
Page 16 and 17: XP is characterized by genetic hete
Page 18: are diagnosed as a collodion baby (
Page 22 and 23: 23. Gerard, M., Fischer, L., Moncol
Page 24 and 25: associatcd with mutations in the DN
Page 27: CHAPTER 2 MOUSE MODELS TO STUDY THE
Page 30: NER DEFICIENCY AND GENOTOXIC SENSIT
Page 34 and 35: XPC-I-p53+1- mice were more aggress
Page 36 and 37: tumor development was absent in a g
Page 38 and 39: [8, 9] reported substantial embryon
Page 41 and 42: in male sterility. As suggested by
Page 43: A point of concern in the extrapola
Page 47: CHAPTER 3 DISRUPTION OF THE MOUSE X
Page 50: INTRODUCTION To counteract the dele
Page 57:
RAD3 and RAD25 protein (the latter
Page 63:
CHAPTER 4 A MOUSE MODEL FOR THE BAS
Page 72 and 73:
Death occurs after a short period o
Page 77:
Table 3. Comparison of the TTDIBEL
Page 81 and 82:
model (UDS, UV survival, pathology,
Page 84 and 85:
33. Stefanini, M., Giliani, S., Nar
Page 88 and 89:
INTRODUCTION Genomic instability is
Page 91:
correlates very well with literatur
Page 96 and 97:
mice, which are histologically noml
Page 98 and 99:
proneness in mice cOlTesponds with
Page 101 and 102:
18, Lehmann, A. R., C. F, Arlclt, B
Page 103:
CHAPTER 6 SYMPTOMS OF PREMATURE AGI
Page 106 and 107:
INTRODUCTION The genome is under co
Page 108 and 109:
osteosclerosis, carly depigmentatio
Page 110:
oocyte that showed gemlinal vesicle
Page 114 and 115:
DISCUSSION Human aging syndromes Ag
Page 116 and 117:
lower levels of the anti-oxidants s
Page 118:
6. Nance, M.A and Ben·y, S.A. (199
Page 121 and 122:
SUMMARY AND CONCLUSIONS DNA damage
Page 123 and 124:
features are due to an impairment o
Page 125:
symptoms in normal aging. Oxidative
Page 130 and 131:
In Hoofdstuk 5 worden experimenten
Page 132 and 133:
LIST OF PUBLICATIONS Bitter, W., va
Page 134 and 135:
DANKWOORD Het schrijven van een dan
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