The Molecular Basis of Sister Chromatid Cohesion

The description of chromosome segregation during cell division reaches back over a century. Abnormal chromosome counts correlate with human malignancies and, already in 1890, Hansemann suggested that aberrant chromosome segregation causes the aberrant behaviour of cancer cells. Meanwhile, we know that replicated sister chromatids are held together by the ring-shaped cohesin complex, forming the basis for their faithful pairwise segregation during cell division. Cohesin topologically embraces sister DNAs, but how does DNA enter cohesin rings? Most importantly, how does cohesin tether exactly the two DNA replication products that are produced in S phase? Here, we propose to innovate molecular experimental tools to answer these central outstanding questions. We will take advantage of recent advances to recapitulate both topological cohesin loading onto DNA, as well as DNA replication, with purified proteins. This will help us understand the process by which cells faithfully pass on chromosomes to their daughters.