Cells frequently experience DNA damage that requires repair by homologous recombination (HR). Proteins involved in HR are carefully coordinated to ensure proper and efficient repair without interfering with normal cellular processes. In Saccharomyces cerevisiae, Rad55 functions in the early steps of HR and is regulated in response to DNA damage through phosphorylation by the Mec1 and Rad53 kinases of the DNA damage response. To further identify regulatory processes that target HR, we performed a high-throughput genetic interaction screen with RAD55 phosphorylation site mutants. Genes involved in the mRNA quality control process, nonsense-mediated decay (NMD), were found to genetically interact with rad55 phospho-site mutants. Further characterization revealed that RAD55 transcript and protein levels are regulated by NMD. Regulation of HR by NMD extends to multiple targets beyond RAD55, including RAD51, RAD54 and RAD57. Finally, we demonstrate that loss of NMD results in an increase in recombination rates and resistance to the DNA damaging agent methyl methanesulfonate, suggesting this pathway negatively regulates HR under normal growth conditions.

Saphenous vein grafts (SVGs), used during coronary artery bypass graft surgery for severe coronary artery disease, are prone to degeneration and occlusion, leading to poor long-term patency compared with arterial grafts. Interventions used to treat SVG disease are susceptible to high rates of periprocedural MI and no-reflow. To minimise complications seen with these interventions, proper stents, embolic protection devices (EPDs) and pharmacological selection are crucial. Regarding stent selection, evidence has demonstrated superiority of drug-eluting stents over bare-metal stents in SVG intervention. The ACCF/AHA/SCA American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions guidelines recommend the use of EPDs during SVG intervention to decrease the risk of periprocedural MI, distal embolisation and no-reflow. The optimal pharmacological treatment for slow or no-reflow remains unclear, but various vasodilators show promise.

Despite its technical challenges, orbital atherectomy appears to be a feasible and safe treatment option for calcified aorto-ostial coronary lesions.

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Percutaneous coronary intervention can lead to vascular access complications that prolong patient hospital stay and costs as well as increase patient morbidity and mortality. Given its ease of use and familiarity, transfemoral access is still the preferred method of approach by many operators. The transfemoral approach is used when large bore access is required or if transradial access is not feasible due to variations in the anatomy of the upper extremity artery. The use of fluoroscopy, ultrasonography, and femoral angiography can help the operator obtain proper arteriotomy of the common femoral artery. Measures to decrease vascular access complications include proper technique, optimal pharmacotherapy, and avoiding the use of arterial sheaths >6 Fr. Optimal pharmacotherapy includes the use of bivalirudin and weight-based unfractionated heparin to avoid supratherapeutic activated clotting times, and to avoid glycoprotein IIb/IIIa inhibitors. When used appropriately, vascular closure devices can decrease the risk of bleeding complications. Randomized trials are needed to confirm these recommendations.