Sundquist W I, Klug A
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Nature. 1989 Dec 14;342(6251):825-9. doi: 10.1038/342825a0.
The telomeric ends of eukaryotic chromosomes are composed of simple repeating sequences in which one DNA strand contains short tracts of guanine residues alternating with short tracts of A/T-rich sequences. The guanine-rich strand is always oriented in a 5'-3' direction towards the end of the chromosome and is extended to produce a 3' overhang of about two repeating units in species where the telomeric terminus is known. This overhang has been implicated in the formation of several unusual intra-and intermolecular DNA structures, although none of these structures has been characterized fully. We now report that oligonucleotides encoding Tetrahymena telomeres dimerize to form stable complexes in solution. This salt-dependent dimerization is mediated entirely by the 3'-terminal telomeric overhang (TT-GGGGTTGGGG) and produces complexes in which the N7 position of every guanine in the overhangs is chemically inaccessible. We therefore propose that telomeric DNA dimerizes by hydrogen bonding between two intramolecular hairpin loops, to form antiparallel quadruplexes containing cyclic guanine base tetrads. These novel hairpin dimers may be important in telomere association and recombination and could also provide a general mechanism for pairing two double helices in other recombinational processes.
真核生物染色体的端粒末端由简单的重复序列组成，其中一条DNA链包含鸟嘌呤残基的短片段与富含A/T的短片段交替排列。富含鸟嘌呤的链总是以5'-3'方向朝向染色体末端，并延伸产生一个3'端突出端，在已知端粒末端的物种中，该突出端约为两个重复单元。尽管这些结构均未得到充分表征，但该突出端与几种异常的分子内和分子间DNA结构的形成有关。我们现在报告，编码四膜虫端粒的寡核苷酸在溶液中会二聚化形成稳定的复合物。这种依赖于盐的二聚化完全由3'末端的端粒突出端（TT-GGGGTTGGGG）介导，并产生复合物，其中突出端中每个鸟嘌呤的N7位置在化学上是不可接近的。因此，我们提出端粒DNA通过两个分子内发夹环之间的氢键二聚化，形成含有环状鸟嘌呤碱基四联体的反平行四链体。这些新型发夹二聚体可能在端粒缔合和重组中起重要作用，并且还可能为在其他重组过程中配对两个双螺旋提供一种通用机制。
