Vaccinia DNA topoisomerase catalyzes the cleavage and re-joining of DNA strands through a DNA-(3'-phosphotyrosyl)-enzyme intermediate formed at a specific target sequence, 5'-(C/T)CCTT downward arrow. The 314 aa protein consists of three protease-resistant structural domains demarcated by protease-sensitive interdomain segments referred to as the bridge and the hinge. The bridge is defined by t...

Electron transfer (ET) processes in DNA are of current interest because of their involvement in oxidative strand cleavage reactions and their relevance to the development of molecular electronics. Two mechanisms have been identified for ET in DNA, a single-step tunneling process and a multistep charge-hopping process. The dynamics of tunneling reactions depend on both the distance between the e...

Non-Homologous End Joining (NHEJ) is an efficient mechanism to repair DNA double-strand breaks. XRCC4 and XLF are two structurally-similar core NHEJ proteins. They can directly interact at the protein-protein level and engage DNA by an unknown mechanism. Here, we use optical tweezers and fluorescence microscopy to visualize XRCC4XLF complexes on DNA in real time. We find that the behavior of XR...

Breakage-fusion-bridge cycles in cancer arise when a broken segment of DNA is duplicated and an end from each copy joined together. This structure then 'unfolds' into a new piece of palindromic DNA. This is one mechanism responsible for the localised amplicons observed in cancer genome data. Here we study the evolution space of breakage-fusion-bridge structures in detail. We firstly consider di...

Breakage-Fusion-Bridge cycles in cancer arise when a broken segment of DNA is duplicated and an end from each copy joined together. This structure then ‘unfolds’ into a new piece of palindromic DNA. This is one mechanism responsible for the localised amplicons observed in cancer genome data. The process has parallels with paper folding sequences that arise when a piece of paper is folded severa...

Although quinolones have been in clinical use for decades, the mechanism underlying drug activity and resistance has remained elusive. However, recent studies indicate that clinically relevant quinolones interact with Bacillus anthracis (Gram-positive) topoisomerase IV through a critical water-metal ion bridge and that the most common quinolone resistance mutations decrease drug activity by dis...