EMBO Fellows Meeting 2012

Maria Ermolaeva
EMBO Fellows Meeting 2012
Systemic effects of tissue specific DNA damage
Abstract
DNA damage inflicted by external and internal insults is a common cause of cancer development. It also
strongly contributes to other pathologies such as degenerative disorders and to the overall process of ageing.
The types of DNA damage produced by different genotoxic stimuli as well as intracellular pathways involved in
damage recognition, damage induced cell cycle arrest and DNA repair have been extensively characterized.
However systemic effects of genome instability are not well understood and it remains unclear how
neighboring tissues or even distant organs respond to localized DNA damage. Some clues about cell-nonautonomous
outcome of genome instability recently came from studying the effect of UV light on the
mammalian skin and through evaluating the consequences of genotoxic anti-tumor therapies. Yet the
mammalian system is too complex to allow unveiling of the putative core mechanisms that mediate cell-nonautonomous
DNA damage response. In our attempt to identify such core mechanisms we employed the
nematode worm C. elegans as the model system. We took advantage of the fact that young adult worms show
clear distinction between post mitotic soma and the germline where mitosis and meiosis occur actively. Due to
indicated cell cycle differences the two compartments have different chromatin and DNA management status
and exhibit distinct sensitivities to DNA damaging agents. The activities of the DNA damage checkpoint
machinery and specific DNA repair pathways are also distinct in the soma and the germline. Therefore by using
particular genotoxic stimuli and/or loss of function mutants for specific repair genes we could generate
genome instability in the specific tissue of C. elegans. We then employed high throughput gene expression
analysis in combination with several transgenic reporter systems based on the expression of a fluorescent
protein to uncover and directly visualize what signaling cascades could be activated by DNA damage in a cellnon-autonomous
manner.
Maria A. Ermolaeva and Bjoern Schumacher
CECAD Cologne. Institute for Genetics, University of Cologne. Zuelpicher Strasse 47a, 50674 Cologne, Germany
14-17 June 2012, Heidelberg, Germany