An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

We study the physiological consequences of DNA damage at the cellular and organismal level mainly, but not exclusively, in mammals. Nuclear DNA damage triggers a signaling and effector pathway known as the DNA damage response (DDR) that coordinates cell-cycle arrest (checkpoint functions) and DNA repair. Persistent DDR signaling establishes cellular senescence, a condition in which cells remain alive but permanently unable to further proliferate. Cellular senescence is important both in the process of organismal ageing and in tumor suppression.

Recently we discovered that the DNA damage response activation is dependent on the generation of short non coding RNAs (named DDRNAs) generated at the site of DNA damage and carrying the sequence of the damaged site. Interfering with the biogenesis or stability of DDRNAs strongly reduces DDR activation and checkpoint enforcement, including cellular senescence.

PhD students involved:

• Flavia Michelini
• Francesca Rossiello
• Giuseppina D'alessandro
• Ubaldo Gioia
• Sofia Francia