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DNA binding by the Rev1 BRCT region : implications for biological and structural function

Groote, F.H. de

Citation

Groote, F. H. de. (2011, February 9). DNA binding by the Rev1 BRCT region : implications for biological and structural function. Retrieved from https://hdl.handle.net/1887/16451

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/16451

Note: To cite this publication please use the final published version (if applicable).

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DNA binding by the Rev1 BRCT region:

Implications for Structural and Biological Function

Proefschrift

Ter verkrijging van

de graad van Doctor aan de Universiteit Leiden

op gezag van Rector Magnificus Prof. Mr. P.F. van der Heijden, volgens besluit van het College voor Promoties

te verdedigen op woensdag 9 februari 2011.

Klokke 15:00 uur

door

Frederik Hendrik de Groote

Geboren te Emmen in 1980

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2

Promotiecommissie

Promotor: Prof.dr. J. Brouwer.

Co-Promotor: Dr. G. Siegal.

Overige leden: Prof.dr. J.E. Sale (Cambridge University, UK) Prof.dr. M. Ubbink.

Dr. J.G. Jansen.

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3

“You live and learn. At any rate, you live!’”

Douglas Adams.

English humorist and science fiction novelist (1952-2001)

Voor mijn (groot)ouders

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4 Cover design: F.H. de Groote

Printed by Wöhrmann Print Service, Zutphen.

ISBN 978-90-8570-719-6 F.H. de Groote 2011

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5

Contents

List of Abbreviations 6

Chapter I General Introduction 9

Chapter II DNA Binding Properties of the Rev1 BRCT Region 53 Chapter III Determination of Amino Acid Requirements for DNA

Binding by the Rev1 BRCT Region 79

Chapter IV Implications of BRCT Mediated DNA Binding:

Cooperative Binding of Two Primer Termini 99 Chapter V Determination of the Cellular Role of the Rfc1 BRCT

Region

117

Chapter VI General Discussion, Conclusion and Future Prospects 139

Summary 151

Samenvatting 154

Dankwoord 158

CV 161

List of publications 162

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List of Abbreviations

9-1-1 Rad9- Rad1- Hus1 Complex 20NT Amino acids 1-20 of Rev1

aa amino acids

BER Base Excision Repair

BRCA1 Breast Cancer Type 1 Susceptibility Protein BPDE Benzo[a]pyrene diolepoxide

BRCT BRCA1 C-Terminal Domain CIP Calf Intestinal Phosphatase CPD Cyclobutane Pyrimidine Dimer DTD Deoxycytidyl Transferase Domain EMSA Electrophoretic Mobility Shift Assay FAN1 Fanconi Associated Nuclease 1 Fen1 Flap Endonuclease 1

HR Homologous Recombination ICL Interstrand Cross link

MCM Mini-Chromosome Maintenance MMR Mismatch Repair

NER Nucleotide Excision Repair NIR Nucleotide Incision Repair NTR N-Terminal Region

ORC Origin Recognition Complex

P Phosphorylated

PAD Polymerase Associated Domain PCNA Proliferating Cell Nuclear Antigen PID Polymerase Interaction Domain

Pol Polymerase

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7 RID Rev1 Interaction Domain RFC Replication Factor C RPA Replication Protein A SDM Site directed mutagenesis SHP Single hairpin

TLS Translesion Synthesis UBM Ubiquitin Binding Motif UBZ Ubiquitin Binding Zinc Finger

WRN Werner Syndrome

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