基于原子力显微镜研究p53蛋白与PBR322 DNA的相互作用

肿瘤(癌症)是由于细胞在复制过程中,DNA损伤不能修复导致细胞凋亡或者细胞无限增殖而形成的。DNA在细胞中转录和翻译都会涉及蛋白与DNA的结合,肿瘤抑制蛋白也是参与这一过程的关键蛋白之一。然而,众多研究发现,肿瘤抑制蛋白p53具有识别和修复损伤DNA的效果,对于细胞的凋亡、基因的保护和避免癌症发生有着重要的意义。有研究表明,金属镁离子和锌离子可以增强p53蛋白的结构稳定性和p53-DNA的亲和力。因此,我们基于原子力显微镜(AFM),直观地呈现出p53蛋白与PBR322环状DNA相互作用的图像,同时发现p53蛋白可以使环状DNA自身形成聚集或者相交。但是,对于长度相当的5 000bp的线状DNA几乎没有这样的效果,而对于20 000bp DNA不会出现这样的现象。然而,在高浓度镁离子环境下,环状DNA会扭转成为麻花状,即形成超螺旋结构。这一现象,可为p53蛋白功能和作用机理研究提供指导,也为癌症治疗、癌症药物开发以及癌症检测方法提供启发。

Study on interaction between p53 protein and PBR322 DNAbased on atomic force microscopy

Tumor (cancer) is caused by the apoptosis or proliferation of cells when DNA damage cannot be repaired in time in the process of replication. The processes of DNA transcription and expression are all involved in the interaction of protein and DNA in living cells. And, tumor suppressor protein is also one of the key proteins involved in this process. However, many studies have found that the tumor suppressor protein p53 can recognize and repair damaging DNA, which plays a significant role in cell apoptosis, gene protection and avoidance of cancer. Studies have shown that the structural stability of p53 protein and the affinity of p53 DNA can be enhanced by metal ions, such as magnesium and zinc ions. Therefore, based on atomic force microscopy (AFM), the interaction image of p53 protein and PBR322 ring DNA is visually presented. And, it is found that p53 protein can promote a ring DNA aggregation or cross in itself. However, this phenomenon occurrence is rare for linear DNA with the length of 5 000bp, and it is not occurrence in 20 000bp DNA either. However, protein p53 can make ring DNA to be a twist shape in high magnesium concentration solution, that is, the supercoil shape is formed. This phenomenon may provide guidance for the study on the function and mechanism of protein p53, as well as provide insights into cancer therapy, cancer drug development and cancer detection methods.