Community Research and Development Information Service - CORDIS


ReStreCa Report Summary

Project ID: 617102
Funded under: FP7-IDEAS-ERC
Country: Switzerland

Periodic Report Summary 3 - RESTRECA (DNA Replication Stress in Cancer)

We have successfully established the physiological relevance of replication fork remodelling in response to numerous cancer chemotherapeutic treatments. We have identified key cellular factors mediating these important transactions at replication forks, implicating in it key signalling pathways so far mostly characterised for the cellular response to DNA breaks. Recently we have a key role for replication fork reversal in promoting fork degradation in homologous recombination-defective tumours, which underlies the exquisite sensitivity of these tumours to cancer chemotherapy.
We have also characterised the peculiar type of replication stress constitutively experienced by embryonic stem cells, during the marked hyper-proliferation that is intrinsically associated with early embryogenesis. We are now in the process to explore whether similar perturbations of the replication process are detectable in adult stem cells, when specific stimuli promote their transient hyper-proliferation to guarantee tissue homeostasis or responses to pathogens.
We have experienced more technical problems in advancing our studies on oncogene-induced replication stress. We have recently refined our experimental strategy and will be focusing on the potential synergy of specific oncogenes and tumour suppressors in respect to genome instability during early tumourigenesis. Meanwhile, we have provided evidence that endogenous sources of replication stress can induce similar fork remodelling events to those extensively characterised as a response to cancer chemotherapeutic treatments

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