Professor Mark Dillingham - University of Bristol

Professor Mark Dillingham

Control of bacterial DNA break repair by phage-encoded DNA mimics

Phage and bacteria are engaged in a constant evolutionary battle for supremacy. Bacteria have evolved diverse anti-phage immunity systems. In response, phage deploy proteins designed to inhibit these systems and optimise bacterial metabolism to better suit the phage lifecycle. These inhibitor proteins often arise from small open reading frames encoding highly acidic proteins which target DNA binding proteins through substrate mimicry. Here, I will discuss three distinctive phage proteins (λ Gam, T7 gp5.9 and P22 Abc2) which all target the RecBCD helicase-nuclease: a complex responsible for initiating DNA break repair by homologous recombination in E. coli. I will present evidence, including high-resolution structures of each protein bound to its target, showing that these proteins inhibit or modify the behaviour of RecBCD using distinctive mechanisms, including mimicry of broken DNA. I will also discuss our recent finding that, in common with other DNA mimic proteins, gp5.9 targets multiple host cell factors. These include the bacterial condensin complex MukBEF, providing the first example of phage interference with DNA segregation in the host.