中文摘要：

采用电喷雾质谱（ESI-MS）和圆二色谱（CD）法研究了Kras基因G-四链体的形成与性质,结果表明,在阳离子条件下,KS1序列形成的是平行构象为主的混合构象G-四链体。实验探索了不同位置G碱基突变对Kras原生型序列G-四链体结构的影响,发现在KS1序列中,第6位G碱基突变对G-四链体影响不大;第13位G碱基突变会导致G-四链体层数减少;而第18、19位G碱基突变会导致G-四链体稳定性下降,同时G-四链体构象也向反平行移动,说明这些位置的G碱基对KS1序列G-四链体的形成有较大的贡献,它们很有可能参与了G-四分体平面的组成,最终形成了特殊的G-四链体结构。虽然不同位置的碱基突变对KS1序列G-四链体的影响各不相同,但突变后的序列形成G-四链体的能力整体比原生型序列弱,这在一定程度上表明,生物体内一部分基因突变后所导致的癌症可能与G-四链体结构的破坏有关。该结果可为G-四链体的结构和生物学功能研究提供更多信息,同时也可为相关抗癌药物的研制提供更广阔的思路和方向。

英文摘要：

G-quadruplexes are special secondary structures of nucleic acids that widely exist in human genome,and it has been suggested that these structures could be involved in many cellular processes,such as gene transcription,cell growth and apoptosis.DNA or RNA that fold into G-quadruplexes are usually guanine-rich sequences,such as human telomere sequence and the promoter regions of certain oncogenes.SinceG-quadruplexes represent potentially important targets in cancer relief and drug development,information about the formation,properties,recognition and biological behaviors of G-quadruplexes may provide useful guidance on tumor prevention and treatment.The Kras gene,which is one of the most important cancer genes,has been found to be closely related to human hepatocellular carcinoma,pancreatic cancer,and so on.Recently more and more studies focused on a nuclease hypersensitive element（NHE）located in the promoter region of Kras,which was upstream of the transcription start site.The G-rich strand of NHE was found to form a G-quadruplex suspected to be involved in transcription regulations.So the G-rich strand d（GGGAAGAGGGAAGAGGGGGAGG）of NHE was chosen as the target.Electrospray mass spectrometry（ESI-MS）and circular dichroism（CD）were used to investigate the formation and conformation characteristics of this G-quadruplex in this paper.The results showed that the native type of Kras sequence（KS1）could fold into stable G-quadruplex structures with three tetrads.Furthermore,the mutant experiment was performed to investigate the contributions of different guanines（G）of KS1 to the formation of G-quadruplexes.The results indicat that the sixth G（from 5＇to 3＇）of KS1don＇t involve in the formation of G-tetrad,and when it is replaced by thymine（T）,the conformation and stability of G-quadruplexes are changed little.On the contrary,the thirteenth,eighteenth and nineteenth G（from5＇to 3＇）,show big differences to the formation of G-tetrads.The mutant would cause the conformation of G-quadru