Introduction
Each cell in the human body receives thousands of DNA lesions per day. DNA lesions can interfere with genome replication and transcription, and if they are not repaired or are repaired incorrectly, they lead to mutations that may threaten cell viability. The most deleterious DNA breaks are the Double Strand Breaks (DSBs) because unfaithful repair can lead to the formation of cancerous chromosomal translocations. It is poorly understood why translocations between chromosomes recur at specific break points in the genome and even less is known about how ends from different DSBs meet in the cell nucleus. It was recently shown that broken chromosome ends are positionally stable and unable to roam the cell nucleus and that unrepaired DSBs preferentially undergo translocations with neighboring chromosomes. In our group we are using a unique cell system to induce DSB at a specific chromosomal location and to follow the fate of damaged DNA in living cells in real time.
The goal of Evi Soutoglou’s research is to investigate the dynamics of DSBs in relation to the surrounding chromatin structure and nuclear architecture and to test how this is related to their repair and their involvement in the formation of chromosomal translocations.
Projects
Research performed in Evi Soutoglou’s lab addresses how DNA repair occurs in the context of chromatin and the highly compartmentalized nucleus. Projects in the lab include:
1/ Investigation of the role of nuclear organization in DNA damage response and the formation of chromosomal translocations
2/ Visualization of the formation of chromosome translocations in vivo using live cell imaging
3/ Identification of novel chromatin related proteins that are involved in the repair of DSBs
4/ Investigation of the dynamics of RNA pol II transcription in response to DSBs
Impact
Centrioles are essential for the formation of several microtubule-organizing structures, including centrosomes, cilia, and flagella. Centrosomes are the major microtubule organizer in animal cells, while cilia and flagella are important in signalling and motility. Abnormalities in microtubule-organising structures and cell polarity have been observed in a variety of human diseases, such as cancer and cystic kidneys. An understanding of the pathways involved in the regulation of microtubule-organising centers formation and cell proliferation will be invaluable to generate diagnostic and prognostic markers, and provide novel therapeutic targets and add to our understanding of basic molecular phenomemon present in our cells.
