Sequence effects in single-base loops for quadruplexes
Sequence effects in single-base loops for quadruplexes
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DOI：
10.1016/j.biochi.2008.01.009
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发表时间：
2008-05-01
期刊：
影响因子：
3.9
通讯作者：
Mergny, Jean-Louis
中科院分区：
文献类型：
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作者：
Guedin, Aurore;De Cian, Anne;Mergny, Jean-Louis
分子内由单链DNA形成的g -四联体引起了人们的极大兴趣，因为它们可能在端粒、癌基因启动子序列和基因组的其他生物学相关区域形成。因此，了解控制这些分子内结构形成的规则并确定它们的稳定性是很重要的。我们在此比较了27个不同的序列，这些序列包含三个鸟嘌呤的四束，具有中等(3)或相对较长的（6-9个碱基）中心环和两个由单个核苷酸H （a， T或C）组成的环，对应于GGGHGGGN(3)-(9)GGGHGGG基序。这些序列类似于重复序列和启动子序列中的序列基序。得到了几个结论：(1)所有序列在钾中（T-m在55℃~ 83℃之间）容易形成非常稳定的四联体；（ii）这些四组分在钠中也能形成，但在Na+和K+的熔化温度相差21 ~ 36℃时，T-m明显降低；（iii）长（9个碱基）中心环对四联体稳定性的有害影响最小；（iv）嘧啶在两个单碱基环中都优于腺嘌呤；(v)钾的折叠拓扑结构相对稳定：所有寡核苷酸的CD谱与全平行链参考四联体的CD谱相匹配；（vi）相反，从CD和电泳结果判断，在钠中折叠是多样的和序列依赖的。(C) 2008 Elsevier Masson SAS。版权所有。
Intramolecular G-quadruplexes formed by a single DNA strand have attracted much interest due to the possibility that they may form in telomeres, oncogene promoter sequences and other biologically relevant regions of the genome. Therefore, it is important to understand the rules that govern the formation of these intramolecular structures and to determine their stabilities. We compared here 27 different sequences containing four tracts of three guanines with a medium (3) or relatively long (6-9 bases) central loop and two loops composed of a single nucleotide H (A, T or C) corresponding to the GGGHGGGN(3)-(9)GGGHGGG motif. These sequences are similar to sequence motifs that can be found in repeated and promoter sequences. Several conclusions were reached: (i) all sequences are prone to form very stable quadruplexes in potassium (T-m between 55 degrees C and 83 degrees C); (ii) these quadruplexes also form in sodium but with a strongly decreased T-m with a 21 to 36 degrees C difference in melting temperature between Na+ and K+; (iii) a long (9 bases) central loop had a minimal deleterious impact on the stability of the quadruplex; (iv) pyrimidines are preferred over adenine in both single-base loops; (v) the folding topology is relatively robust in potassium: the CD spectra of all oligonucleotides matched the one of all-parallel stranded reference quadruplexes; (vi) conversely, in sodium the folding is diverse and sequence-dependent, as judged from CD and electrophoresis results. (C) 2008 Elsevier Masson SAS. All rights reserved.