Broadcast: Events

DNA damage response activation is dependent on functional transcriptional promoters assembly at DNA ends

Wednesday 5 February 13:00 until 14:00
GDSC Seminar Room
Speaker: Dr Fabrizio d'Adda di Fagagna, IFOM, The FIRC Institute of Molecular Biology, Milan
Part of the series: GDSC Seminar Series

Our group has reported that DNA double-strand breaks (DSBs) trigger the synthesis of damage-induced long non-coding RNA (dilncRNA) that can be processed into shorter DNA damage response RNAs (DDRNAs) (Francia et al Nature 2012, Michelini et al Nature Cell Biology 2017, Pessina F. et al. Nature Cell Biology 2019). Such transcripts are essential for full DNA damage response (DDR) activation and their inhibition by antisense oligonucleotides (ASO) allows site-specific DDR inhibition. 

We will extend these observations to the biology of telomeres and indicate how dysfunctional telomeres recapitulates events observed at DSB and that ASOs against such telomeric dilncRNAs and DDRNAs inhibit DDR activation at telomeres (Rossiello et al. Nature Communications 2017) and thus allow for the first time to determine the contribution of telomeric DDR in physiological and pathological contexts (Aguado et al. Nature Communications 2019), with the potential to merge as a therapeutic approach.

All welcome to attend.


By: Sarah Frances
Last updated: Wednesday, 15 January 2020