Structural studies of herpesvirus proteins involved in DNA replication – this is the title of a project by Dr Małgorzata Figiel from the Laboratory of Protein Structure.  Recently she has received a grant from the National Science Center. The amount of it is PLN 2,047,255 and it will be carried out over a period of 4 years. Congratulations!

The aim of the project is to improve a better understanding of the DNA replication process in herpesviruses, which are one of the most widespread pathogens found in humans. Admittedly, they pose little threat to healthy individuals, but they can cause severe disease in immunocompromised patients.

Despite a wealth of biochemical data on herpesvirus replication proteins, our understanding of herpesvirus DNA replication is still incomplete. No structures have yet been determined for several of the replication proteins. Furthermore, unclear is how replication proteins are recruited to the replication fork and how the synthesis of both DNA strands is coupled. Finally, structural information about interactions of proteins that form HSV-1 replication machinery with each other and with their nucleic acid substrates is missing, so the architecture of the complete replisome or even its parts is unknown.

The research team, led by Dr. Figiel, plans to determine atomic structures of herpesvirus proteins involved in DNA replication and their complexes with relevant nucleic acid substrates using cryo-electron microscopy (cryo-EM) and X-ray crystallography. These structural studies will be complemented by biochemical experiments. – Based on the structures and the biochemical data we will reveal how the herpesvirus replisome works and how the activity of its components is regulated and coordinated. The results of this project will be a valuable resource for future efforts that seek to produce new anti-herpesvirus drugs – adds dr Małgorzata Figiel.