Sequence effects in single-base loops for quadruplexes

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• 作者：Aurore Gu&#xe9 ; din ; Anne De Cian ; Julien Gros ; Laurent Lacroix ; Jean-Louis Mergny
• 关键词：DNA ; Unusual DNA structure ; Sequence effects ; Thermodynamics ; G-quartet
• 刊名：Biochimie
• 出版年：2008
• 期刊代码：24_03009084
• 类别：bio
• 出版时间：May 2008
• 卷：90
• 期：5
• 页码：686-696
• 文件大小：1435 K

摘要

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_3–9GGGHGGG 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 °C and 83 °C); (ii) these quadruplexes also form in sodium but with a strongly decreased T_m, with a 21 to 36 °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.