In E. coli our work concentrated on analysis of protein complexes to shed light on regulation in polymerase switching events, crucial to both replication and repair. Accurate DNA repair mechanisms exist to ensure damage is repaired prior to replication, although some will always remain at the time of replication. These present a hazard to the replicative polymerase and can lead to fork stalling, with potentially disastrous consequences for the cell. Cells employ a family of low fidelity translesion polymerases which can bypass these hazardous lesions, although at a cost, as bypass is frequently mutagenic.

Much of our work focused on the E. coli DNA polymerase IV (Pol IV), which has been implicated in the adaptive processes of bacterial pathogens and the acquisition of antibiotic resistance. Its human homologue, Pol kappa, is known to enhance genomic instability when inappropriately regulated and has been implicated in several cancer types.

My structure of the C-terminal little finger domain of Pol IV in complex with the beta-clamp was the first structural demonstration that sliding clamps were capable of binding two proteins simultaneously (Bunting et al. 2003, EMBO J). It additionally identified a previously unknown regulatory interface that regulates access of Pol IV to the replication fork, thereby limiting its mutagenic activity.

We have also shown that the binding motif of Pol V shows a unique interaction the with beta-clamp (Patoli et al., 2013).

Research in H. volcanii