- Author
-
I. de Krijger
- Title
- Control of repair activities at DNA double strand breaks and telomeres
- Supervisors
-
M.M.S. van Lohuizen
- Co-supervisors
-
J.J.L. Jacobs
- Award date
- 15 February 2021
- Number of pages
- 246
- ISBN
- 9789464191103
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
The DNA in our cells, storing the information that every cell needs to perform its specific function, needs to be carefully protected. Various sources, both externally and from inside the cell, constantly threaten the integrity of the DNA, causing DNA damage. DNA double strand breaks (DSBs) are the most detrimental to the cell, and lack of repair, or incorrect repair of such breaks can lead to cell death. Moreover, incorrect repair can introduce errors in the DNA such as mutations or chromosomal rearrangements, resulting in genomic instability which can eventually contribute to the development of cancer. Cells have therefore developed mechanisms that detect the damage and ensure rapid and correct DNA repair, and this is collectively referred to as the ‘DNA damage response’. Importantly, the ends of natural chromosomes resemble DSBs, but repair activities at chromosome-ends would have severe consequences for genome integrity. The ends of chromosomes are therefore protected by specialized structures known as telomeres. The aim of this thesis is to increase our understanding of how repair activities at DSBs and telomeres are controlled. For this we used various methods aiming at identifying novel proteins that act in the DNA damage response and mechanistically understand their function.
- Persistent Identifier
- https://hdl.handle.net/11245.1/09288626-31b6-4a80-9d7d-51d16fcd0d65
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: Introduction: Control of repair activities at DNA double strand breaks and telomeres
Chapter 2: H3K36 dimethylation by MMSET promotes classical non-homologous end-joining at unprotected telomeres
Chapter 3: CHD2 and H3.3 promote NHEJ at deprotected telomeres
Chapter 4: H4K20me2 distinguishes pre-replicative from post-replicative chromatin to appropriately direct DNA repair pathway choice by 53BP1-RIF1-MAD2L2
Chapter 5: MAD2L2: Jack of many trades
Chapter 6: Inhibition of end-resection in G1 by MAD2L2
Chapter 7: Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells
Addendum I: CTC1 facilitates NHEJ at unprotected telomere-ends
Chapter 8: MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair
Chapter 9: General discussion
Summary; Samenvatting
Curriculum vitae; PhD portfolio; List of publications; Acknowledgements
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