Dr Martina Foglizzo

Introduction

DNA replication relies on the regulated assembly and disassembly of replisome factors on chromatin. The 55LCC complex functions as a four-membered assembly that specifically interacts with lagging strand replisome components to promote protein unfolding during replication stress. Martina was awarded a Discovery Fellowship by the Biotechnology and Biological Sciences Research Council (BBSRC) to understand the molecular and mechanistic basis of how 55LCC complex assembly directs substrate recruitment and regulates 55LCC enzymatic function. To achieve this, Martina applies a combination of structural and biochemical methods, reinforced with biophysical, computational and cell-based techniques.

Current major projects include

• How are 55LCC ATPase and unfoldase activities regulated?
• How does 55LCC associate with its substrates?

Detailed Research Programme

We focus on the characterisation of the 55LCC ATPase/unfoldase complex, a key macromolecular machine essential for regulating DNA replication. Mutations in 55LCC result in complex instability and loss of function, giving rise to rare neurological and neurodevelopmental syndromes as well as proteostasis-related diseases, cancers and ribosomopathies. We combine biochemical, biophysical, structural, computational and cell-based techniques to understand how 55LCC complex assembly and function are regulated at the molecular, structural and mechanistic levels. Our multi-disciplinary approach has the potential to provide important insights on a new protein quality control mechanism that is essential for genome stability.