Torsional stress. The DNA double helix has one major problem that we know from telephone cords: it is difficult to untangle. However, our DNA is constantly twisted and untangled for gene transcription. This constant twisting and untwisting produces torsional stress that is relieved by topoisomerases. A recent publication in Nature Genetics now identified a human neurological phenotype that is caused by faulty activity of this mechanism: neurodegeneration with epileptic encephalopathy. However, there are some features of the phenotype that are not easily explained by erroneous DNA twisting. Continue reading
Tag Archives: inhibitory synapse
SHANK3, epilepsy, and the excitatory/inhibitory imbalance
Postsynaptic. SHANK proteins are elements of the postsynaptic density, linking synaptic transmission with the cytoskeleton. Deletions in SHANK2 and SHANK3 are known genetic risk factors for a broad range of neurodevelopmental disorders. The role of the reciprocal duplications, however, has remained unclear. In recent paper in Nature, a novel mouse model expressing a SHANK3 transgene is investigated. The results of a mere 1.5 fold overexpression of the protein are dramatic, hinting at unanticipated mechanisms that regulate the balance between excitation and inhibition. Continue reading
