端粒DNA形成不同构象的关键因素

The key factors in conformation of telomeric DNA

端粒DNA与细胞的衰老、死亡、癌变密切相关,人体端粒DNA富含G和C单链可分别形成G-四链体(G-quadruplex)和I-motif四链体结构。它们与端粒酶活性、着丝粒DNA、RNA夹层结构等有直接关系,且可作为药物的靶点,因此研究其形成条件有重要意义。本文用圆二色谱谱研究富G和C单链及其混合状态下形成不同四链构象的关键影响因素。结果表明,dAG3(T2AG3)3是否形成G-quadruplex主要取决于溶液中金属阳离子,d(C3TA2)3C3T形成I-motif则与溶液pH密切相关,而在dAG3(T2AG3)3/d(C3TA2)3C3T混合溶液中很易形成双螺旋(duplex)结构,在一定条件下也可形成G-quadruplex、I-motif混合态。

Telomeres are closely related to cell aging, death and canceration. Guanine-rich and cytosine-rich strands of human telomeric DNA can form G-quadruplex and I-motif conformation, respectively. These conformations have relations with telomerase activity, centromeric DNA structures, RNA intercalated structures, having been an attractive drug target for cancer chemotherapy and for modulation of gene transcription. In this paper, key factors to the formation of different conformations are studied by using circular dichroism spectrum （CDS）. The results show that the formation of dAG3（T2AG3）3 into G-quadruplex is greatly affected by metal ions, while the I-motif structure of d（CaTA2）3CaT depends largely on pH values. It is easy to form WC duplex structure in the equimolar mixture of dAG3（T2AG3）3 and d（C3TA2）3C3T, however, G-quadruplex and I-motif can both exist under certain conditions.