Periodic Reporting for period 3 - CRYOREP (Chromosome Replication Visualised by Cryo-EM)
Período documentado: 2022-03-01 hasta 2023-08-31
Our achievements will hopefully lead to describing the molecular mechanism of DNA replication at atomic resolution. By understanding how the replication machinery works, we will be able to explain how to intervene when things go wrong in this process. Describing a the cascade of events that lead to chromosome replication is important in and of itself, as it explains the process which stands at the core of the perpetuation of life. Importantly, these studies will also provide new knowledge that can be used for the development of anti-cancer therapeutic agents.
We now are making significant progress towards understanding how the MCM helicase is activated to start opening the double helix. These achievements will put us in an excellent position to understand how DNA is synthesised by a large macromolecular machine including the MCM helicase and the replicative polymerases. Likewise, we will now start studying how DNA, which in our cells is wrapped around structural proteins conferring physical stability to our genome, can become accessible to the helicase to allow unwinding. The end result of our study will be a molecular movie of chromosome replication.