PhD defence Z. (Zeliha) Yalçin

Brief summary of the doctoral thesis:

Telomeres protect the ends of chromosome. When telomeres lose their protective function, chromosome ends will inappropriately be recognized as damaged DNA. This results in a so-called DNA-damage response and activation of DNA-repair mechanisms. Unfortunately, at deprotected telomeres this results in even more DNA-damage and this promotes genomic instability, which contributes to the development of cancer. In our research we identify and characterize new proteins that are part of the ubiquitin machinery and that play a role in this DNA-damage response. Ubiquitination is a modification on proteins that, amongst others, leads to the degradation of the modified protein or a change in its function. We studied whether removing the newly identified proteins could prevent the unwanted repair of deprotected telomeres. Furthermore, we investigated how these proteins play a role in the DNA-damage response and repair at deprotected telomeres. By increasing our knowledge about how cells respond to loss of telomere deprotection and the role of ubiquitination in this, we hope to be able to identify targetable factors to prevent the development of cancer and improve the treatment of cancer.