A single G-to-C change causes human centromere TGGAA repeats to fold back into hairpins.
A single G-to-C change causes human centromere TGGAA repeats to fold back into hairpins.
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DOI：
10.1073/pnas.93.22.12159
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发表时间：
1996-10
影响因子：
11.1
通讯作者：
Leiming Zhu;S. Chou;B. Reid
中科院分区：
文献类型：
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作者：
Leiming Zhu;S. Chou;B. Reid
最近，我们发现，在人类染色体的着丝粒上，卫星III (TGGAA)n串联重复序列与自身配对，形成一种不寻常的“自互补”反平行双工结构，其中含有（GGA）2基序，其中来自相反链的两个未配对的鸟嘌呤插入剪切的G.A碱基对之间。在单独的研究中，我们也已经确定GCA三重态不会形成双分子（GCA）2基序，而是促进含有GCA-turn基序的发夹的形成，其中环包含由剪切的G.A对关闭的单个胞苷。由于TGCAA是卫星III重复序列中发现的最常见的TGGAA变体，我们推断该变体形成GCA-turn迷你循环折叠结构的潜力可能是调节天然（TGGAA）n重复序列中局部结构的重要因素。我们在这里报道了核磁共振衍生的七十脱氧核苷酸(G)TGGAATGCAATGGAA(C)的溶液结构，其中一个中心TGCAA五聚体两侧是两个TGGAA五聚体。这种17-mer形成了一个相当不寻常且非常稳定的发夹结构，在茎中包含8个碱基对，其中只有4个是沃森-克里克对，以及一个由单个胞苷残基组成的环。茎部包含一个（GGA）2基序，在两个剪切的G.A碱基对之间插入14G/4G堆叠；阀杆的环端由一个剪切8G组成。10A闭合对，9C环的胞嘧啶碱基堆叠在8G上。这种不寻常的发夹结构（Tm = 63°C）的显著稳定性表明，它可能在调节着丝粒上卫星III (TGGAA)n重复序列的折叠中起重要作用。
Recently, we established that satellite III (TGGAA)n tandem repeats, which occur at the centromeres of human chromosomes, pair with themselves to form an unusual "self-complementary" antiparallel duplex containing (GGA)2 motifs in which two unpaired guanines from opposite strands intercalate between sheared G.A base pairs. In separate studies, we have also established that the GCA triplet does not form bimolecular (GCA)2 motifs but instead promotes the formation of hairpins containing a GCA-turn motif in which the loop contains a single cytidine closed by a sheared G.A pair. Since TGCAA is the most frequent variant of TGGAA found in satellite III repeats, we reasoned that the potential of this variant to form GCA-turn miniloop fold-back structures might be an important factor in modulating the local structure in natural (TGGAA)n repeats. We report here the NMR-derived solution structure of the heptadecadeoxynucleotide (G)TGGAATGCAATGGAA(C) in which a central TGCAA pentamer is flanked by two TGGAA pentamers. This 17-mer forms a rather unusual and very stable hairpin structure containing eight base pairs in the stem, only four of which are Watson-Crick pairs, and a loop consisting of a single cytidine residue. The stem contains a (GGA)2 motif with intercalative 14G/4G stacking between two sheared G.A base pairs; the loop end of the stem consists of a sheared 8G.10A closing pair with the cytosine base of the 9C loop stacked on 8G. The remarkable stability of this unusual hairpin structure (Tm = 63 degrees C) suggests that it probably plays an important role in modulating the folding of satellite III (TGGAA)n repeats at the centromere.