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THE ROLE OF NON-CODING RNA IN THE CELLULAR RESPONSE TO DNA DAMAGE

 

Aging and the onset of tumors have in common the accumulation of DNA damage. DNA is constantly exposed to the risk of damage caused by natural radiations, free radicals and by mistakes occurring during transcription and replication of DNA itself. To respond to such a dangerous and frequent event, cells have evolved highly sophisticated molecular mechanisms that, taken together, are called the DNA Damage Response (DDR). DDR defects, indeed, cause an increase in the frequency of mutations and exacerbate the genomic instability, which fuel tumorigenesis and premature aging in various animal models.




Fig 1.: Foci of DDR proteins recruited at DNA damage sites.


The new research group of Fabrizio d'Adda di Fagagna at IGM-CNR, Pavia, studies how DDR is modulated by small RNA molecules generated at the damaged site. Our recent finding published in Nature in 2012 (http://www.ncbi.nlm.nih.gov/pubmed/22722852), in fact, has opened a new field of research: the role of RNA in the maintenance of genomic stability. We already know that the RNAs involved in DDR, which we named DDRNAs, are non-coding RNAs characterized by a length between 22 and 30 nucleotides. They derive from transcripts of the damaged chromosomal locus and are processed by the endonucleases DROSHA and DICER, previously characterized for their involvement in the RNA interference pathway. We also know that DDRNAs act in murine and human cells, both normal and tumoral, and also at the level of an entire living organism such as zebrafish (Danio rerio).




Fig 2.: DDR proteins recruited to DNA lesion in a DDRNAs-dependent manner.


The group of IGM-CNR now intends to characterize the processes of biogenesis and the mechanisms of functioning of DDRNAs throughout the genome of human cells and to study their impact on relevant biological phenomena such as aging and cancer.

The laboratory at the IGM in Pavia will work closely with the laboratory at IFOM in Milan (http://www.ifom-ieo-campus.it/research/dadda.php  www.ifom.eu/it/ricerca-cancro/ricercatori/fabrizio-d-adda-di-fagagna/).

 

 

Short curriculum Vitae of Fabrizio d’Adda di Fagagna

 

Contacts:

Sofia Francia: tel +39 0382 546325; email: sofia.franciaigm.cnr.it

Fabrizio d'Adda di Fagagna: tel. +39 02 574303.227; email: fabrizio.daddaigm.cnr.it  

 





 

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