Final Report Summary - CHROMOSOME STABILITY (Coordination of DNA replication and DNA repair at single-forks: the role of the Smc5-Smc6 complex in replication fork stalling and resumption)
The main focus of the research has been the development of biochemical approaches to identify sites of post-translational modification by the small ubiquitin-like modifier SUMO that were dependent on the SUMO E3 ligase Nse2. Following the initial identifications, we investigated the functional significance in some of these targets, namely Scc1,a subunit of the cohesin complex, and Sgs1, the Bloom helicase homologue, which causes Bloom Syndrome (a cancer prone genetic disorder in humans). We have demonstrated that Scc1 SUMOylation by Nse2 is required for repair of a DNA double strand break. On he functional role of Sgs1 SUMOylation our results demonstrate that it is involved in the resolution of recombination intermediates that appear during DNA replication at stalled or damaged forks.
We also made an unexpected discovery while studying damaged replication forks. We developed our observation and were able to show that during mitosis there is an alteration of the DNA winding status that requires attachments of the spindles to kinetochores and the Condensin complex that promotes decatenation by topoisomerase II.
We also made an unexpected discovery while studying damaged replication forks. We developed our observation and were able to show that during mitosis there is an alteration of the DNA winding status that requires attachments of the spindles to kinetochores and the Condensin complex that promotes decatenation by topoisomerase II.