Rigo Riccardo, Sissi Claudia
Department of Pharmaceutical and Pharmacological Sciences, University of Padova , Via Marzolo 5, 35131 Padova, Italy.
Biochemistry. 2017 Aug 22;56(33):4309-4312. doi: 10.1021/acs.biochem.7b00660. Epub 2017 Aug 8.
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.
c-KIT的近端启动子包含一个特殊结构域，该结构域由三个紧密相邻的富含鸟嘌呤的短序列组成，这些序列可折叠成称为G-四链体（G4）的非经典DNA二级结构。在此，我们聚焦于一个包含两个连续G4（kit2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，将它们插入延伸序列后仍保留折叠成G4的能力。在此，我们强调了两个形成单元之间存在串扰。这种先前未被探索的G4-G4相互作用调节了c-KIT启动子整体排列的构象和稳定性。它并非由单个核苷酸的堆积所支持，而是指一个被两核苷酸环包围的G4-G4相互作用表面，这可能代表了一个可靠的前所未有的抗癌治疗靶点。
