Characterization of G4-G4 Crosstalk in the c-KIT Promoter Region
Characterization of G4-G4 Crosstalk in the c-KIT Promoter Region
复制标题
DOI：
10.1021/acs.biochem.7b00660
复制
发表时间：
2017-08-22
期刊：
影响因子：
2.9
通讯作者：
Sissi, Claudia
中科院分区：
文献类型：
--
作者：
Rigo, Riccardo;Sissi, Claudia
c-KIT的近端启动子包含一个特殊的结构域，该结构域由三个短的富含G的序列组成，这些序列靠近在一起，并且可以折叠成称为G-四链体（G4）的非经典DNA二级结构。在这里，我们集中于含有两个连续的G4（kit 2和kit*）的序列。通过电泳、表面等离子体共振和光谱技术，我们证明了它们在插入延伸序列后保留折叠成G4的能力。在这里，我们强调了两个成型单元之间串扰的发生。这种以前未探索的G4-G4相互作用调节c-KIT启动子整体排列的构象和稳定性。它不支持单核苷酸的堆叠，而是指由两个核苷酸环包围的G4-G4相互作用表面，这可能代表抗癌治疗的可靠的前所未有的靶点。
The proximal promoter of c-KIT contains a peculiar domain that consists of three short G-rich sequences that are close together and can fold into noncanonical DNA secondary structures called G-quadruplexes (G4). Here, we focused on a sequence containing two consecutive G4 (kit2 and kit*). By electrophoretic, surface plasmon resonance, and spectroscopic techniques, we demonstrated that they retain the ability to fold into G4 upon being inserted into the extended sequence. Here, we highlighted the occurrence of crosstalk between the two forming units. This previously unexplored G4-G4 interaction modulates both the conformation and the stability of the overall arrangement of the c-KIT promoter. It is not supported by stacking of single nucleotides but refers to a G4-G4 interaction surface surrounded by a two-nucleotides loop that might represent a reliable unprecedented target for anticancer therapy.