Advancing Epigenetics Towards Systems Biology

Fabrizio D'Adda Di Fagagna

The FIRC Institute of Molecular Oncology (IFOM)

The role of DDRNAs, a novel class of short non coding RNAs, in DNA damage response (DDR) control

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fabrizio d adda di fagagna

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

Latest publications

DICER, DROSHA and DNA damage-response RNAs are necessary for the secondary recruitment of DNA damage response factors.

26906421 - 2016-02-26
J Cell Sci 2016 Feb 16;

Francia S, Cabrini M, Matti V, Oldani A, d'Adda di Fagagna F

Human nuclear ARGONAUTE 2 interacts in vivo only with small RNAs and not with DNA.

25970378 - 2015-05-15
Cell Cycle 2015 Jul 3;14(13):2001-2

Gioia U, d'Adda di Fagagna F

Notch is a direct negative regulator of the DNA-damage response.

25895060 - 2015-04-22
Nat Struct Mol Biol 2015 May;22(5):417-24

Vermezovic J, Adamowicz M, Santarpia L, Rustighi A, Forcato M, Lucano C, Massimiliano L, Costanzo V, Bicciato S, Del Sal G, d'Adda di Fagagna F

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