Project description DEENESFRITPL Fundamental mechanisms of chromosome replication Faithful duplication and transmission of genetic and epigenetic information inside living cells are conducted by large macromolecular complexes known as the replisomes, which coordinate the enzymatic events during chromosome duplication. The EU-funded REPLISOMEBYPASS project aims to develop a single-molecule imaging approach to study the mechanisms by which replisomes maintain efficiency and coordination during collisions with obstacles on the chromosome. The project capitalises on a recently developed multidimensional, single-molecule imaging approach for the real-time visualisation of coordination during replication. The objective is to understand the consequences of replisome collisions and the mechanisms that allow bypassing or triggering replication fork collapse. The project’s work will uncover the molecular origin of chromosome damage underlying many diseases. Show the project objective Hide the project objective Objective Faithful duplication and transmission of genetic and epigenetic information is the most vital cellularfunction for the preservation and proliferation of life. In cells, this process is conducted by largemacromolecular complexes, known as replisomes, that coordinate the sequence of enzymatic eventsduring chromosome duplication. While recently developed single-molecule techniques promiseunprecedented access to the complex inner workings of these sophisticated machines, most studiesconducted have focused on individual factors, operating on non-physiological substrates, which hasprovided an incomplete molecular picture.My recent development of a multidimensional, single-molecule imaging approach that allowsfor real-time visualisation of coordination during replication represents a significant breakthroughin our ability to study macromolecular machines in vitro. Building on this success, here I describesingle-molecule imaging approaches to address one of the long-standing questions in chromosomebiology: How do replisomes maintain efficiency and coordination during collisions with obstacleson the chromosome?Our objective is to develop a complete molecular understanding of the consequences ofreplisome collisions and the underlying mechanisms that allow for bypass or trigger replication forkcollapse. We will begin this long-term research effort by addressing several issues fundamental tochromosome replication: How does replisome coordination and composition change duringencounters with topological barriers in chromosomes? What are the dynamic events that underlienucleosome disassembly by histone chaperones during replication? How does the eukaryoticreplisome collaborate with histone chaperones to ensure faithful inheritance of epigeneticinformation encoded on histones?These studies will provide a framework for understanding the dynamics of replisome collisionsand the molecular origin of chromosome damage underlying many diseases. Fields of science natural sciencesbiological sciencesmolecular biologymolecular geneticsnatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigenetics Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-STG - ERC Starting Grant Call for proposal ERC-2018-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Net EU contribution € 1 500 000,00 Address HOFGARTENSTRASSE 8 80539 Munchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 500 000,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Germany Net EU contribution € 1 500 000,00 Address HOFGARTENSTRASSE 8 80539 Munchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 500 000,00
