The cover image depicts an analogy often used by teachers of molecular genetics courses when describing slipped-strand DNA: DNA is like a zipper made of two strands, Watson and Crick. Usually, the zippers’ teeth pair perfectly, but in repetitive DNAs, the zipper can get jammed by misaligned pairing of the teeth, thus producing slipped-DNA structures. Slipped DNAs formed by disease-causing CAG/CTG-repeating DNAs can be incorrectly repaired and can consequently yield repeat mutations, which are known to cause at least 17 human neurodegenerative and neuromuscular diseases, such as Huntington’s disease (HD). Ongoing repeat expansions arise in affected tissues and contribute to disease onset, progression and severity. Arresting or reversing somatic repeat expansions should arrest or reverse disease onset, progression and severity. In HD model mice, a small molecule that targets the expansion process by specifically binding slipped-CAG repeats can induce contractions of the expanded repeat in the striatum, a vulnerable brain region in people with HD. Essentially, this treatment can reverse the disease-causing repeat expansions.
See Nakamori et al.