Mechanism三核苷酸重复扩增机制.pdfVIP

# Acta Genetica Sinica, January 2006, 33 (1): 1-11 ISSN 0379-4172 Mechanism of Trinucleotide Repeats Instabilities: The Neces- sities of Repeat Non-B Secondary Structure Formation and the Roles of Cellular Trans-acting Factors PAN Xue-Feng 1 . Institute of Cell and Molecular Biology, Edinburgh University, Edinburgh EH9 3JR, UK; 2. School of Life Sciences Technology, Beijing Institute of Technology, Beijing 10008 1, China Abstract: The mechanism underlying CAGCTG CGGCCG and GAA.TTC trinucleotide repeats expansion and contraction insta- bilities 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 forma- tion and the repeats expansion in vivo. Although longer trinucleotide repeats may be theoretically easier to form non-B DNA sec- ondary 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. Key words: trinucleotide repeats; expansion and contraction instability; fragility; human neurological-muscular disease; trans-acting factor Trinucleotide repeats array distributed exclu- sively in human genome, however the biological sig- nificance of these distributions has not been clearly understood. It is now known that expansio