Controllo della attività di ATM da parte di RNA generati da DICER e DROSHA
- 3 Anni 2012/2015
- 210.600€ Totale Fondi
When studying the mechanisms of action of ATM, the protein mutated in AT patients, we unexpectedly discovered that RNA is essential for its proper functioning. More specifically we found that at DNA double-strand breaks (the events that trigger ATM activation) long molecules of RNA are generated that are then processed in shorter ones. These RNAs then pair between them and this pairing is essential for the activation of ATM. This discovery reveals for the first time an unexpected level of regulation of this protein and a new mechanism of protection of the integrity of the genome.
Pubblicazioni Scientifiche
- 2015 EMBO JOURNAL
Telomerase abrogates aneuploidy-induced telomere replication stress, senescence and cell depletion
- 2013 STEM CELL REP
DNA Damage in Mammalian Neural Stem Cells Leads to Astrocytic Differentiation Mediated by BMP2 Signaling through JAK-STAT
- 2014 CELL DEATH AND DIFFERENTIATION
Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation
- 2015 NATURE STRUCTURAL & MOLECULAR BIOLOGY
Notch is a direct negative regulator of the DNA-damage response
- 2017 AGING CELL
A novel single-cell method provides direct evidence of persistent DNA damage in senescent cells and aged mammalian tissues
- 2016 JOURNAL OF CELL SCIENCE
DICER, DROSHA and DNA damage response RNAs are necessary for the secondary recruitment of DNA damage response factors
- 2015 CELL CYCLE
Human nuclear ARGONAUTE 2 interacts in vivo only with small RNAs and not with DNA
- 2014 CURRENT OPINION IN GENETICS & DEVELOPMENT
Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing
- 2014 TRENDS IN CELL BIOLOGY
A direct role for small non-coding RNAs in DNA damage response
- 2017 NATURE COMMUNICATIONS
DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs
- 2012 NATURE CELL BIOLOGY
Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation
- 2015 ELIFE
Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae
- 2012 CELL DEATH AND DIFFERENTIATION
Differential regulation of DNA damage response activation between somatic and germline cells in Caenorhabditis elegans
- 2015 EMBO REPORTS
RNA-processing proteins regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA
- 2017 NATURE COMMUNICATIONS
A damaged genome's transcriptional landscape through multilayered expression profiling around in situ-mapped DNA double-strand breaks
- 2014 PLOS ONE
Stable Cellular Senescence Is Associated with Persistent DDR Activation