Objective Faithful chromosomal DNA replication is essential to maintain genome stability. A number of DNA metabolism genes are involved at different levels in DNA replication. These factors are thought to facilitate the establishment of replication origins, assist the replication of chromatin regions with repetitive DNA, coordinate the repair of DNA molecules resulting from aberrant DNA replication events or protect replication forks in the presence of DNA lesions that impair their progression. Some DNA metabolism genes are present mainly in higher eukaryotes, suggesting the existence of more complex repair and replication mechanisms in organisms with complex genomes. The impact on cell survival of many DNA metabolism genes has so far precluded in depth molecular analysis. The use of cell free extracts able to recapitulate cell cycle events might help overcoming survival issues and facilitate these studies. The Xenopus laevis egg cell free extract represents an ideal system to study replication-associated functions of essential genes in vertebrate organisms. We will take advantage of this system together with innovative imaging and proteomic based experimental approaches that we are currently developing to characterize the molecular function of some essential DNA metabolism genes. In particular, we will characterize DNA metabolism genes involved in the assembly and distribution of replication origins in vertebrate cells, elucidate molecular mechanisms underlying the role of essential homologous recombination and fork protection proteins in chromosomal DNA replication, and finally identify and characterize factors required for faithful replication of specific vertebrate genomic regions.The results of these studies will provide groundbreaking information on several aspects of vertebrate genome metabolism and will allow long-awaited understanding of the function of a number of vertebrate essential DNA metabolism genes involved in the duplication of large and complex genomes. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomes Programme(s) 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) Topic(s) ERC-CG-2013-LS1 - ERC Consolidator Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2013-CoG See other projects for this call Funding Scheme ERC-CG - ERC Consolidator Grants Coordinator UNIVERSITA DEGLI STUDI DI MILANO Address Via festa del perdono 7 20122 Milano Italy See on map Region Nord-Ovest Lombardia Milano Activity type Higher or Secondary Education Establishments Principal investigator Vincenzo Costanzo (Dr.) Administrative Contact Annalisa Brengola (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITA DEGLI STUDI DI MILANO Italy EU contribution € 132 000,00 Address Via festa del perdono 7 20122 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Higher or Secondary Education Establishments Principal investigator Vincenzo Costanzo (Dr.) Administrative Contact Annalisa Brengola (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data IFOM-ISTITUTO FONDAZIONE DI ONCOLOGIA MOLECOLARE ETS Italy EU contribution € 1 867 800,00 Address Via adamello 16 20139 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Research Organisations Administrative Contact Carlo Raimondi Cominesi (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
