Usdin K
Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA.
Nucleic Acids Res. 1998 Sep 1;26(17):4078-85. doi: 10.1093/nar/26.17.4078.
Tandem repeats of certain trinucleotides show extensive intergenerational instability in humans that is associated with a class of genetic disorders known as the Triplet Expansion Diseases. This instability is thought to be a consequence of the formation of intrastrand structures, including hairpins, triplexes and tetraplexes, by the tandem repeats. I show here that CGG-repeats which are associated with this group of diseases, and AGG- and TGG-repeats which are not currently known to be, form several intrastrand structures including tetraplexes. In all cases the tetraplexes have the same overall conformation in which all the G residues are involved in G4-tetrads. CGG-repeats also form stable hairpins, but AGG- and TGG-repeats do not form hairpins of comparable stability. However, since tetraplexes can be thought of as folded hairpins, many of the properties ascribed to disease-associated triplets that form hairpins, may apply to these sequences as well. The fact that AGG- and TGG-repeats are not currently associated with any triplet expansion disease suggests either that the ability to adopt an intrastrand folded structure is not sufficient for expansion, or that other diseases associated with such triplets might remain to be identified.
某些三核苷酸的串联重复序列在人类中表现出广泛的代际不稳定性，这与一类被称为三联体扩增疾病的遗传疾病有关。这种不稳定性被认为是串联重复序列形成链内结构（包括发夹结构、三链体和四链体）的结果。我在此表明，与这类疾病相关的CGG重复序列，以及目前未知与之相关的AGG和TGG重复序列，会形成包括四链体在内的几种链内结构。在所有情况下，四链体都具有相同的整体构象，其中所有的G残基都参与形成G4-四联体。CGG重复序列也会形成稳定的发夹结构，但AGG和TGG重复序列不会形成具有可比稳定性的发夹结构。然而，由于四链体可以被认为是折叠的发夹结构，许多归因于形成发夹结构的与疾病相关的三联体的特性，可能也适用于这些序列。AGG和TGG重复序列目前与任何三联体扩增疾病都没有关联，这一事实表明，采用链内折叠结构的能力对于扩增来说是不够的，或者与这类三联体相关的其他疾病可能仍有待发现。
