GLORI

Global analysis of R-loop structures (RNA-DNA hybrids) by advanced microscopic and genetic approaches

Coordinatore	DEBRECENI EGYETEM    more  Organization address address: EGYETEM TER 1 city: DEBRECEN postcode: 4032 contact info Titolo: Prof. Nome: Gabor Cognome: Szabo Email: send email Telefono: 36412623
Nazionalità Coordinatore	Hungary [HU]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2011-CIG
Funding Scheme	MC-CIG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-12-01   -   2016-11-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	DEBRECENI EGYETEM  Organization address address: EGYETEM TER 1 city: DEBRECEN postcode: 4032 contact info Titolo: Prof. Nome: Gabor Cognome: Szabo Email: send email Telefono: 36412623	HU (DEBRECEN)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Genetic alterations from point mutations to chromosome rearrangements are usually associated with pathological disorders. Unraveling the origin of such events was greatly enhanced by the discovery of cis-acting factors (e.g. chromosomal fragile sites, G quadruplexes) behaving as chromosomal hotspots for genomic instability, but a detailed mechanistic understanding of their mode of action has remained elusive. Most current models of genomic instability incorporate R-loops - nucleic acid structures in which an RNA strand displaces one strand of a duplex DNA molecule for a limited length - as immediate cause of gene rearrangements. The present application is based on prior observations of the host laboratory on previously unrecognized ribonucleoprotein particles containing RNA-DNA hybrids, being positioned at loop-size intervals in the chromatin of lower and higher eukaryotic cells (Szekvolgyi L et al., PNAS, 2007). The molecular identity and the cell biological significance of the revealed structures are unknown. The goal of this project is to unravel the molecular structure and epigenetic landscape of the regularly spaced ribonucleoprotein complexes containing RNA-DNA hybrids previously described by our laboratory, with a special emphasis on their connection to chromatin loop domain formation and genetic recombination. We expect that our work plan - proposing the global analysis of R-loop structures using a range of cell biophysical and genetic approaches in the genetically tractable model organism S cerevisiae as well as in various human cell lines - will yield novel data relevant to the rules that govern not only normal chromatin architecture but also an RNA-DNA hybrid-mediated pathological scenario leading to chromosomal rearrangements.'