Genome control by cohesin ligands (360G-Wellcome-302868_Z_23_Z)

The organisation of mammalian genomes in 3D nuclear space is critical for genome function. The cohesin complex is a key player in this organisation. Cohesin extrudes DNA loops, accumulates at specific genomic sites, and adopts distinct structural and functional states that link genome topology to genomic processes. These include transcription, replication, repair, recombination, sister chromatic cohesion and chromosome segregation. How cohesin controls such diverse biological processes is a major question in genome biology. Addressing this knowledge gap is important because the processes coordinated by cohesin are central to human development, homeostasis and disease. Here we address how cohesin controls genomic processes and how cohesin function is regulated by a network of interacting proteins. We propose to address these aims by a collaborative, interdisciplinary approach that combines our expertise in structural biology, biochemistry, cell biology, model organisms and integrative imaging across scales. This will link atomic structures to molecular mechanisms and organismal functions.