Kudlicki Andrzej S
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas, United States of America.
PLoS One. 2016 Jan 4;11(1):e0146174. doi: 10.1371/journal.pone.0146174. eCollection 2016.
The G-quadruplex is a non-canonical DNA structure biologically significant in DNA replication, transcription and telomere stability. To date, only G4s with all guanines originating from the same strand of DNA have been considered in the context of the human nuclear genome. Here, I discuss interstrand topological configurations of G-quadruplex DNA, consisting of guanines from both strands of genomic DNA; an algorithm is presented for predicting such structures. I have identified over 550,000 non-overlapping interstrand G-quadruplex forming sequences in the human genome--significantly more than intrastrand configurations. Functional analysis of interstrand G-quadruplex sites shows strong association with transcription initiation, the results are consistent with the XPB and XPD transcriptional helicases binding only to G-quadruplex DNA with interstrand topology. Interstrand quadruplexes are also enriched in origin of replication sites. Several topology classes of interstrand quadruplex-forming sequences are possible, and different topologies are enriched in different types of structural elements. The list of interstrand quadruplex forming sequences, and the computer program used for their prediction are available at the web address http://moment.utmb.edu/allquads.
G-四链体是一种非经典的DNA结构，在DNA复制、转录和端粒稳定性方面具有重要生物学意义。迄今为止，在人类核基因组的背景下，仅考虑了所有鸟嘌呤均来自DNA同一条链的G4结构。在此，我将讨论由基因组DNA两条链上的鸟嘌呤组成的G-四链体DNA的链间拓扑结构；并提出了一种预测此类结构的算法。我在人类基因组中鉴定出超过550,000个非重叠的链间G-四链体形成序列——显著多于链内结构。对链间G-四链体位点的功能分析显示与转录起始密切相关，结果与XPB和XPD转录解旋酶仅结合具有链间拓扑结构的G-四链体DNA一致。链间四链体在复制起始位点也有富集。链间四链体形成序列存在几种拓扑类别，不同的拓扑结构在不同类型的结构元件中富集。链间四链体形成序列列表以及用于预测它们的计算机程序可在网址http://moment.utmb.edu/allquads获取。
