MODEL SYSTEMS TO IDENTIFY GENES AND FACTORS IN THE SIGNAL TRANSDUCTION PATHWAY DEFECTIVE IN ATAXIA TELANGIECTASIA PATIENTS
- 3 Anni 2003/2006
- 170.900€ Totale Fondi
La syndrome ereditaria Ataxia telangiectasia (AT) (e sindromi affini quali ATLD e NBS) determina disturbi neurologici, disfunzioni immunologiche e predisposizione all’insorgenza tumorale. AT e’ causata da mutazioni nel gene ATM evulutivamente molto conservato e coinvolto nei processi di riparazione delle lesioni cromosomali.
ATM e’ stato implicato in altri processi cellulari e in particolare nel metabolismo mitocondriale.
In questo progetto intendiamo identificare e caratterizare geni umani coinvolti nei processi controllati da ATM. Abbiamo gia’identificatom alcuni di questi geni. E’ interessante notare che tali geni codificano funzioni muitocondriali e la loro caratterizzazione e’ in corso.
I risultati di questo studio potrebbero contribuire ad elucidare I difetti molecolari che determinano AT e in particolare a comprendere le cause dei disturbi neurologici di questi pazienti.
Pubblicazioni Scientifiche
- 2003 MOLECULAR CELL
Branch migrating sister chromatid junctions form at replication origins through Rad51/Rad52-independent mechanisms
- 2006 EXPERIMENTAL CELL RESEARCH
The Rad53 signal transduction pathway: Replication fork stabilization, DNA repair, and adaptation
- 2004 NATURE
DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1
- 2008 GENES & DEVELOPMENT
Cohesion by topology: sister chromatids interlocked by DNA
- 2005 MOLECULAR AND CELLULAR BIOLOGY
Srs2 and Sgs1 DNA helicases associate with mrell in different subcomplexes following checkpoint activation and CDK1-mediated Srs2 phosphorylation
- 2006 CELL
Ubc9-and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks
- 2005 MOLECULAR CELL
Exo1 processes stalled replication forks and counteracts fork reversal in checkpoint-defective cells
- 2005 GENES & DEVELOPMENT
Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase
- 2007 GENES & DEVELOPMENT
Top1- and Top2-mediated topological transitions at replication forks ensure fork progression and stability and prevent DNA damage checkpoint activation
- 2007 DNA REPAIR
Interplay of replication checkpoints and repair proteins at stalled replication forks
- 2007 GENES & DEVELOPMENT
RecQ helicases queuing with Srs2 to disrupt Rad51 filaments and suppress recombination