Rebecca Ley

The role of phosphorylation in regulating the activity of human flap endonuclease 1

After graduating from the University of Sheffield with a masters degree in Chemistry in 2015 I decided to remain in the department to study for a PhD. I am working in the Department of Chemistry in the research group of Prof Jane Grasby where I study the phosphorylation of Flap Endonuclease 1.

Flap Endonuclease 1 (FEN1) is a 5’-nuclease which plays a role in Okazaki Fragment Maturation during lagging strand DNA synthesis, and in DNA repair. The phosphorylation of human FEN1 by cyclin dependent kinases was first reported in 2003 in a paper which concluded that phosphorylation affects both the activity of FEN1 and its ability to bind to Proliferating Cell Nuclear Antigen (PCNA) which is known to coordinate replication fork proteins. Subsequently, the effects of the phosphorylation of FEN1 have been studied both in vitro and in vivo, along with links between phosphorylation and other post-translational modifications. Despite this, the picture of FEN1 phosphorylation is still not clear, and the aim of my project is to establish on which amino acids FEN1 can be phosphorylated and the effects this modification has on the activity and interactions of the enzyme.