Structural basis of mitotic chromosome condensation

• Applicant: Professor Dr. Christian H. Häring
• Subject Area: Cell Biology
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 226492122

Successful segregation of a cells genetic material during cell divisions depends on the formation of highly structured chromosomes at the onset of mitosis and meiosis. A key player for this re-organization of chromatin fibers is a conserved multi-subunit protein complex named condensin, which is composed of a heterodimer of SMC (structural maintenance of chromosomes) coiled-coil proteins, a kleisin protein, and two additional HEAT-repeat containing subunits. It has been proposed that condensin functions by stabilizing loops through the entrapment of DNA helices within the large tripartite ring structure formed by its SMC and kleisin subunits. How the complex recognizes its DNA substrate and how DNA may be transported into the ring remains, however, unknown. Here we propose a multidisciplinary approach to gain insight into condensins interaction with chromosomes. Using a combination of biochemical, structural, and cell biological methods, we aim to reconstitute condensin binding to DNA with defined components in vitro, dissect the contribution of individual condensin subunits in recruiting condensin to chromosome fibers, identify the nature of the interaction with DNA at atomic resolution, and investigate the role of this interaction for condensin function during chromosome segregation in living cells. Insights into the detailed molecular machinery responsible for the organization of mitotic chromosome structure will be essential for our understanding how cells prevent chromosome missegregation.

• DFG Programme: Research Grants