How ‘unfinished business’ from S-phase impacts on chromosome segregation in mitosis

How ‘unfinished business’ from S-phase impacts on chromosome segregation in mitosis

Speaker: Professor Ian Hickson, University of Copenhagen

We study regions of the human genome that are inherently difficult to replicate, such as chromosomal fragile sites. These so-called ‘enemies within the genome’ are conserved in evolution but seem to create endless problems for cells by triggering genome rearrangements and faulty chromosome segregation in mitosis. This is particularly prevalent in human cancers. We showed recently that DNA replication remains incomplete at fragile sites even after cells have entered mitosis, whereupon an emergency form of DNA synthesis occurs. Incomplete replication leads to the persistence of DNA connections (ultra-fine bridges) between the segregating sister chromatids in mitosis. Our latest attempts to model mitotic sister chromatid disjunction using optical tweezers will be discussed.