BSc (Sheffield), PhD (Birmingham)
Protein-DNA interactions, Investigation of enzymes carrying out reactions on nucleic acids, Enzymology, DNA synthesis, Biophysical methods (fluorimetry, calorimetry).
Read-ahead recognition of uracil by archaeal DNA polymerases.
Archaeal polymerases are unable to copy template-strand uracil and stall replication on encountering this base. Uracil, in DNA, arises from the deamination of cytidine in C:G base-pairs to give a pro-mutagenic U:G mis-pair. Replication past uracil irreversibly fixes the mutation and results in a C:G to T:A transition. Stalling undoubtedly serves to protect the archaeal genome from the mutagenic potential of uracil; a problem expected to be especially acute for many of these organisms due to their high temperature environments, conditions which promote cytidine deamination.
Currently we are investigating the factors underlying the specific recognition of uracil by archaeal DNA polymerases and attempting to elucidate the post-stalling events that, eventually, eliminate uracil from the genome.
Research into read-ahead recognition of uracil, within our group, is currently funded by the BBSRC, European Union and Cancer Research UK.