Community Research and Development Information Service - CORDIS


RSHEALTH Report Summary

Project ID: 617840
Funded under: FP7-IDEAS-ERC
Country: Spain

Mid-Term Report Summary - RSHEALTH (Investigating the causes and consequences of replication stress in mammalian health)

In RSHEALTH our goal is to explore how problems that arise during DNA replication (also known as replication stress (RS)) can ultimately lead to pathologies such as cancer or accelerated ageing, and to use that information to explore new strategies to limit these problems. During the initial period of our grant, our laboratory has contributed in many relevant areas of this proposal. For instance, in what relates to ageing, we revealed that an extra production of nucleotides extends the lifespan of mice suffering from accelerated ageing. In the context of cancer, we have mostly with inhibitors of the RS-response kinase ATR, which we previously developed and shown that they present increased toxicity for cancer cells, in vitro. During this period, our work in this area has been focused in two main questions: (a) identifying which tumor types preferentially benefit from a therapy with ATR inhibitors, and (b) defining mechanisms of resistance that might emerge to the treatment. We now have published our findings in these two fronts, and keep working on them to further investigate the anticancer potential of this strategy. Finally, we have also made significant contributions in other areas such as in the impact of RS in pluripotent cells, in the discovery of a code that regulates how proteins are recruited to sites of DNA replication, or in finding additional examples of how alterations in DNA replication complexes lead to disease in mammals.

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