Objective Duplication of the genome and its division into two daughter cells during mitosis is vital for survival of the organism. Cells have multiple mechanisms to ensure that this process is accomplished correctly thereby preserving the integrity of the genome. The final check before cell division is made by the NoCut abscission pathway. In yeast and animal cells, this mechanism monitors completion of chromosome separation, delaying abscission when chromosome bridges spanning the division site are detected. Aurora B is essential for NoCut function, and several of its targets in this pathway have been identified. In budding yeast, NoCut can be triggered by bridges caused by defects in chromosome condensation, decatenation and replication but importantly not by dicentric chromosome bridges. This suggests that structural features of chromatin bridges are essential to generate the NoCut signal. We will investigate the molecular basis of this differential bridge recognition and the signalling pathway acting upstream of Aurora B. We will define the composition of fine and ultra-fine chromatin bridges during cytokinesis in human cells at unprecedented resolution by super-resolution microscopy using dSTORM imaging. In parallel, we will use budding yeast to investigate the role of DNA binding proteins as sensors in the NoCut pathway. We will then establish the significance of these findings in human cells, by assaying the function of putative homologs in NoCut, and their localization in chromatin bridges by dSTORM. By combining approaches in two model systems we will define both the molecular and physical constrains for NoCut activation upstream of the established components of the NoCut pathway.Chromosome instability is associated with many human tumours and in some cases with advanced disease making the detailed characterization of this pathway relevant in our understanding of both basic cellular processes and human disease. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesphysical sciencesopticsmicroscopysuper resolution microscopynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticschromosomes Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator FUNDACIO CENTRE DE REGULACIO GENOMICA Net EU contribution € 158 121,60 Address Carrer doctor aiguader 88 08003 Barcelona Spain See on map Region Este Cataluña Barcelona 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 Other funding € 0,00
