My lab is interested in the mechanisms that alleviate arrested DNA replication and the impact their loss has on mutagenesis and on the maintenance of epigenetic memory through the recycling of histones during replication.
Replication can be arrested by DNA damage or by naturally occurring DNA secondary structures. We are particularly interested in translesion synthesis (TLS), which is mediated by specialised DNA polymerases and which is required for replication of both DNA damage and a particular secondary structure called a G quadruplex. Although TLS is potentially mutagenic it plays a critical role in normal cells and understanding its control is central to understanding cell transformation.
We study these processes using the powerful combination of vertebrate somatic cell genetics coupled with biochemical, biophysical and advanced optical microscopy techniques to monitor the molecular choreography of proteins and DNA at sites of stalled replication.