ATMMACHINE
"Structural mechanism of recognition, signaling and resection of DNA double-strand breaks"
| Coordinatore | LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | Germany [DE] |
| Totale costo | 2˙498˙019 € |
| EC contributo | 2˙498˙019 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2012-ADG_20120314 |
| Funding Scheme | ERC-AG |
| Anno di inizio | 2013 |
| Periodo (anno-mese-giorno) | 2013-05-01 - 2018-04-30 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Organization address
address: GESCHWISTER SCHOLL PLATZ 1 contact info |
DE (MUENCHEN) | hostInstitution | 2˙498˙019.00 |
| 2 |
LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Organization address
address: GESCHWISTER SCHOLL PLATZ 1 contact info |
DE (MUENCHEN) | hostInstitution | 2˙498˙019.00 |
Mappa
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Obiettivo del progetto (Objective)
'DNA double-strand breaks are perhaps the most harmful DNA damages and result in carcinogenic chromosome aberrations. Cells protect their genome by activating a complex signaling and repair network, collectively denoted DNA damage response (DDR). A key initial step of the DDR is the activation of the 360 kDa checkpoint kinase ATM (ataxia telangiectasia mutated) by the multifunctional DSB repair factor Mre11-Rad50-Nbs1 (MRN). MRN senses and tethers DSBs, processes DSBs for further resection, and recruits and activates ATM to trigger the DDR. A mechanistic basis for the activities of the core DDR sensor MRN has not been established, despite intense research over the past decade. Our recent breakthroughs on structures of core Mre11-Rad50 and Mre11-Nbs1 complexes enable us now address three central questions to finally clarify the mechanism of MRN in the DDR:
- How does MRN interact with DNA or DNA ends in an ATP dependent manner? - How do MRN and associated factors such as CtIP process blocked DNA ends? - How do MRN and DNA activate ATM?
We will employ an innovative structural biology hybrid methods approach by combining X-ray crystallography, electron microscopy and small angle scattering with crosslink mass spectrometry and combine the structure-oriented techniques with validating in vitro and in vivo functional studies. The anticipated outcome will clarify the structural mechanism of one of the most important but enigmatic molecular machineries in maintaining genome stability and also help understand the molecular defects associated with several prominent cancer predisposition and neurodegenerative disorders.'