title: Mechanism of trinucleotide repeats instabilities: the necessities of repeat non-B secondary structure formation and the roles of cellular trans-acting factors.
abstract: The mechanism underlying CAG.CTG CGG.CCG and GAA.TTC trinucleotide repeats expansion and contraction instabilities has not been clearly understood. Investigations in vitro have demonstrated that the disease causing repeats are capable of adopting non-B secondary structures that mediate repeats expansion. However, in vivo, similar observations have not been easily made so far. Investigations on the non-B secondary structure formation using E.coli, yeast etc cannot simulate the suggested repeats expansion instability. These could leave a space to infer a disassociation of the suggested repeats non-B secondary structure formation and the repeats expansion in vivo. Although longer trinucleotide repeats may be theoretically easier to form non-B DNA secondary structures in replication or in post-replication, however such non-B secondary structures are likely to cause repeat fragility rather than repeat expansion. In fact, repeat expansion as seen in patients may not necessarily require trinucleotide repeats to form non-B secondary structures, instead the repeat expansions can be produced through a RNA transcription-stimulated local repeat DNA replication and a subsequent DNA rearrangement.
authors.affiliation: Institute of Cell and Molecular Biology, Edinburgh University, Edinburgh EH9 3JR, UK. xuefengpancam@yahoo.com.cn
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Pan
mesh_terms: D005600:Fragile X Syndrome / Q000235:genetics / Q000503:physiopathology; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D053842:Microsatellite Instability; D008957:Models, Genetic; D010009:Osteochondrodysplasias / Q000235:genetics / Q000503:physiopathology; D015534:Trans-Activators / Q000502:physiology*; D019680:Trinucleotide Repeat Expansion; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D015534:Trans-Activators