Genotoxic stress and Cancer - Institut Curie / CNRS UMR 3348

Unit Director: Mounira Amor-Guéret

Keywords: DNA replication, DNA recombination, DNA repair, DNA helicases, Bloom Syndrome

The "Genotoxic Stress and Cancer" unit is located on the "Raymond Latarjet" campus of the Institut Curie in Orsay. Under joint supervision with the CNRS and in partnership with the Paris-Sud-11 University, it is composed of approximately 40 people including 26 permanent staff members, organized in 5 groups (a call for applications is currently open to recruit a sixth group).

We focus our work mainly on the mechanisms that are involved in maintaining genome integrity known to play a major role in preventing cancer. The prevention of genetic instability depends on a complex network of pathways induced in response to DNA damage and stalled replication forks, including cell cycle checkpoints, DNA repair systems and apoptosis. Mutations that affect DNA damage response (DDR) pathways have been found to be associated with many human genetic diseases characterized by strong genomic instability and a predisposition to develop cancer. Characterization of DDR pathways is thus an essential issue to tackle carcinogenesis processes. Our unit is composed of five groups that share a common scientific interest in the relationship between DDRs and genome stability. Different aspects of this issue are addressed using a great variety of technological approaches, ranging from traditional techniques of molecular and cell biology, as well as biochemistry, to more sophisticated approaches involving cell and molecular imaging or DNA molecular combing, as well as several model systems such as Saccharomyces cerevisiae and Schizosaccharomyces pombe yeasts, as well as mammalian cells. More specifically, we focus our studies on providing insight on mechanisms that induce genome instability in response to oxidative stress (Huang, Lambert and Sage groups) or in response to stalled replication forks (Amor-Guéret and Lambert groups), and on characterizing the biochemical and biophysical mechanisms of action in response to genotoxic stress (Xi group). The ultimate goal behind the different approaches is to provide insight on the functional relationships between the 3 R's (Replication, Repair and Recombination). We consider basic research as the major source of knowledge and discovery. Yet we are particularly interested in the contribution of our research in the development of cancer diagnosis and treatment techniques. Moreover, each group is conscious of the interest and the urgency of making their know-how available to study environmental agents that are likely to alter genome integrity and to participate in preventing the risks induced by these agents, even in low quantities.

Group(s):

• Cell response to replication stress
  Group leader: Sarah Lambert
• Genetic instability and carcinogenesis
  Group leader: Mounira Amor-Guéret
• Genome stability and genotoxic stress
  Group leader: Meng-Er Huang
• Group Biology of radiations
  Group leader: Evelyne Sage
• Relationship between structures and functions of RecQ family helicases and their roles in genomic integrity and cancer development
  Group leader: Xu-Guang Xi

Platform(s):

• Cell and tissue imaging - UMR 3348 (Pict-IBiSA)
  Leader: Fabrice Cordelières