Objectif Secondary structures such as G-quadruplexes (G4s) can form within DNA or RNA. They pose a dramatic risk for genome stability, because due to their stability they can block DNA replication and this could lead to DNA breaks. In certain cancer cells mutations/deletions are observed at G4s, if a helicase that is important for G4 unwinding is mutated. Nevertheless, G4s are also discussed to be functional elements for cellular processes such as telomere protection, transcription, replication, and meiosis. The aim of this research proposal is to use various biochemical and computational tools to determine which proteins are essential for formation and regulation of G4s. Proposed experiments will gain insights into both “effects” of G4s, the risk for genome stability and its significant function for the cell. In aim 1 we will elucidate and identify novel proteins that bind, regulate, and repair G4s, especially in the absence of helicases, in vitro and in vivo. Our focus is to understand how G4s become mutated in the absence of helicases, which proteins are involved, and how genome stability is preserved. In aim 2, we will use cutting edge techniques to identify regions that form G4s in vivo. Although there is experimental proof for G4s in vivo, this is not commonly accepted, yet. We will provide solid data that will support the existence of G4s in vivo. Furthermore, we will survey genome-wide when and why G4s become a risk for genome stability. Aim 3 will focus on the in silico observation that G4 structures are connected to meiosis. In this aim we will use a combination of techniques to unravel the biological significance of G4s during meiosis in vivo.Due to the connection of G4s and cancer the data obtained from this research proposal will not only be important to understand G4 regulation and formation, but will also provide unique knowledge on the impact of G4 structures for genome stability and thereby for human health. Champ scientifique natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesgeneticshereditynatural sciencesbiological sciencesgeneticsgenomes Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-StG-2014 - ERC Starting Grant Appel à propositions ERC-2014-STG Voir d’autres projets de cet appel Régime de financement ERC-STG - Starting Grant Institution d’accueil UNIVERSITATSKLINIKUM BONN Contribution nette de l'UE € 1 119 382,12 Adresse VENUSBERG-CAMPUS 1 53127 Bonn Allemagne Voir sur la carte Région Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 119 382,12 Bénéficiaires (3) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire UNIVERSITATSKLINIKUM BONN Allemagne Contribution nette de l'UE € 1 119 382,12 Adresse VENUSBERG-CAMPUS 1 53127 Bonn Voir sur la carte Région Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 119 382,12 JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG Participation terminée Allemagne Contribution nette de l'UE € 0,00 Adresse SANDERRING 2 97070 Wuerzburg Voir sur la carte Région Bayern Unterfranken Würzburg, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total Aucune donnée ACADEMISCH ZIEKENHUIS GRONINGEN Participation terminée Pays-Bas Contribution nette de l'UE € 412 242,88 Adresse HANZEPLEIN 1 9713 GZ Groningen Voir sur la carte Région Noord-Nederland Groningen Overig Groningen Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 412 242,88