Control of ATM activity by DICER and DROSHA RNA products
- 3 Years 2012/2015
- 210.600€ Total Award
Studiando i meccanismi di attivazione di ATM, la proteina mutata nei pazienti A-T, abbiamo inaspettatamente scoperto che l’RNA e’ essenziale per il suo corretto funzionamento. Piu’ specificatamente abbiamo scoperto che ai siti di rottura del DNA (l’evento scatenante l’attivazione di ATM) si generano lunghe molecole di RNA che poi vengono processate in piu corte. Questi RNA poi si appaiano tra loro e questo appaiamento e’ essenziale per l’attivazione di ATM. Questa scoperta rivela per la prima volta un livello inaspettato di regolazione di questa proteina ed un nuovo meccanismo di protezione dell’integrita’ del genoma.
Scientific Publications
- 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