Biochemical Characterization of a Structure-Specific Resolving Enzyme from Sulfolobus islandicus Rod-Shaped Virus 2

Sulfolobus islandicus rod shaped virus 2 (SIRV2) infects the archaeon Sulfolobus islandicus at extreme temperature (70°C–80°C) and acidity (pH 3). SIRV2 encodes a Holliday junction resolving enzyme (SIRV2 Hjr) that has been proposed as a key enzyme in SIRV2 genome replication. The molecular mechanism for SIRV2 Hjr four-way junction cleavage bias, minimal requirements for four-way junction cleavage, and substrate specificity were determined. SIRV2 Hjr cleaves four-way DNA junctions with a preference for cleavage of exchange strand pairs, in contrast to host-derived resolving enzymes, suggesting fundamental differences in substrate recognition and cleavage among closely related Sulfolobus resolving enzymes. Unlike other viral resolving enzymes, such as T4 endonuclease VII or T7 endonuclease I, that cleave branched DNA replication intermediates, SIRV2 Hjr cleavage is specific to four-way DNA junctions and inactive on other branched DNA molecules. In addition, a specific interaction was detected between SIRV2 Hjr and the SIRV2 virion body coat protein (SIRV2gp26). Based on this observation, a model is proposed linking SIRV2 Hjr genome resolution to viral particle assembly

At the coalface and the cutting edge: general practitioners’ accounts of the rewards of engaging with HIV medicine

The interviews we conducted with GPs suggest that an engagement with HIV medicine enables clinicians to develop strong and long-term relationships with and expertise about the care needs of people living with HIV ‘at the coalface’, while also feeling connected with a broader network of medical practitioners and other professionals concerned with and contributing to the ever-changing world of science: ‘the cutting edge’. The general practice HIV prescriber is being modelled here as the interface between these two worlds, offering a rewarding opportunity for general practitioners to feel intimately connected to both community needs and scientific change