Dr Matthew Day

Matthew Day

Lecturer in Biochemistry

School of Biological and Behavioural Sciences
Queen Mary University of London
ORCID

Research

Structural biology, CryoEM, Alphafold, DNA replication, DNA repair, Cancer

Interests

DNA replication must occur once, and only once, during each cell cycle. In eukaryotic cells this process is carried out by the replisome, a massive protein machine with many components. The MCM helicase is loaded at origins of replication in an inactive confirmation and must be converted to its active form by a highly coordinated process of events for individual origins to fire and for replication to successfully progress. This is driven by the recruitment of additional protein factors and much of this control is aided by scaffold proteins, such as TOPBP1, bringing the required factors together at the right time.

As well as having to be duplicated, the DNA in our cells is subject to damage every day and must be repaired to maintain genomic stability. DNA repair also requires the coordinated recruitment of multiple protein factors to sites of DNA damage to first recognise, stabilise, mark, and finally repair the damage. Again, large scaffold proteins, including TOPBP1, play important roles in many of these processes.

Research in our group explores the mechanistic details of these processes, with a focus on TOPBP1, through a combination of structural biology (e.g. cryogenic electron microscopy, x-ray crystallography and in silico modelling), biophysical (e.g. fluorescence polarisation and isothermal calorimetry) and other protein and nucleic acid biochemical techniques.