Mechanism for accurate, protein-assisted DNA annealing by Deinococcus radiodurans DdrB.

Accurate pairing of DNA strands is essential for repair of DNA double-strand breaks (DSBs). How cells achieve accurate annealing when large regions of single-strand DNA are unpaired has remained unclear despite many efforts focused on understanding proteins, which mediate this process. Here we report the crystal structure of a single-strand annealing protein [DdrB (DNA damage response B)] in complex with a partially annealed DNA intermediate to 2.

Crystal structure of the DdrB/ssDNA complex from Deinococcus radiodurans reveals a DNA binding surface involving higher-order oligomeric states.

The ability of Deinococcus radiodurans to recover from extensive DNA damage is due in part to its ability to efficiently repair its genome, even following severe fragmentation by hundreds of double-strand breaks. The single-strand annealing pathway plays an important role early during the recovery process, making use of a protein, DdrB, shown to greatly stimulate ssDNA annealing. Here, we report the structure of DdrB bound to ssDNA to 2.

A double-blind, delayed-start trial of rasagiline in Parkinson's disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes.

Background: The ADAGIO study investigated whether rasagiline has disease-modifying effects in Parkinson's disease. Rasagiline 1 mg per day, but not 2 mg per day, was shown to be efficacious in the primary analysis. Here, we report additional secondary and post-hoc analyses of the ADAGIO study.

Clinical pharmacology tyramine challenge study to determine the selectivity of the monoamine oxidase type B (MAO-B) inhibitor rasagiline.

Rasagiline is a selective, monoamine oxidase (MAO)-B inhibitor indicated for treatment of Parkinson's disease. This double-blind, placebo-controlled study determined the tyramine sensitivity factor (TSF) and degree of MAO-A inhibition (ie, reduction in plasma dihydroxyphenylglycol) in healthy volunteers who received phenelzine (15 mg, 3 times daily; positive control), selegiline (5 mg, twice daily), or rasagiline (1-6 mg, once daily) for 14 days or rasagiline 2 mg/d for 30 days. The selegiline/rasagiline groups were randomized to placebo or active drug.