Cancer Network Zurich – Cancer Biology Ph.D. Program

 
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Institute of Molecular Cancer Research
University of Zurich
Y 17 K 84
Winterthurerstrasse 190
8057 Zurich
Phone +41 44 635 34 77 Email

Aykut Murat

Main Field(s) of Research, Abstract
Error-free duplication of DNA and proper segregation of chromosomes are crucial for the viability of an individual cell. In order to maintain genomic stability, cells have developed monitoring systems that detect problems such as damaged DNA and improperly attached chromosomes. These so-called checkpoint mechanisms prevent cell cycle transition if prerequisites for progression have not been met. Upon encountering DNA damage in S-phase or under conditions of replication fork stalling, a replication checkpoint is activated that dramatically slows down the rate of DNA synthesis and thus S phase progression. In replication checkpoint-deficient budding yeast, disturbances caused by DNA damaging agents possibly result in fork collapse or DNA breaks/rearrangements. Previous studies from our and other laboratories showed that in hydroxyurea (HU)-treated yeast cells, 14-3-3 proteins are recruited to DNA replication forks and contribute to control the activity of Exonuclease-1 (Exo1), which would otherwise threaten their integrity. These studies also highlighted the fact that additional unknown targets of 14-3-3 proteins contribute to promote fork progression, stability and restart. My doctoral work will focus on assessing the molecular mechanism of 14-3-3 proteins function at stalled replication forks in order to control DNA replication. Considering that 14-3-3 proteins have already established roles in human diseases, my studies will help expanding our knowledge on pathways controlled by 14-3-3 proteins, possibly offering novel targets in cancer therapy.

Main Fields of Research, Keywords
Cell cycle, replication forks, replicative stress, yeast genetics

Special Techniques and Equipment
S. cerevisiae handling, standard molecular biology techniques (molecular cloning, western blot, southern blot, IP assays), synchronization experiments, 2D gel electrophoresis