DNA 同源重组中DNA超螺旋性及DNA/RAD51 3D网络对DNA同源匹配影响的研究

DNA Double strand DNA breaks (DSBs), including spontaneously programmed and unexpectedly un-programmed DSBs, are high frequent events in organism. DNA homologous recombination (HR) is main approach for high-fidelity gene repair. In meiosis, HR is one of the critical players in chromosomal cross-over which is of the great significance in the propagation of the human being and gene diversity. In the other side, the involvement of HR in un-programmed DNA damage is critically important for gene stability and circumvention of gene mutations inducing the variety of diseases including cancer. Some aspects of DNA HR, especially the procedure of homologous pairing in HR, is still unclear though the extensive researches have been carried out. The further investigation has to be followed-up. The applicant of this proposal focuses on the DNA pairing for a couple of years aboard and hope to deepen the understanding of the mechanism of DNA pairing via this project, so as to develop the novel therapeutic strategy for the diseases targeting the gene repair, such as cancer.

DNA Double strand DNA breaks (DSBs) 是生物体中高频率出现的事件，有内源的程序化的DNA DSBs，也有外源环境损伤造成的DNA DSBs。DNA同源重组是生物体内高保真地修复DSBs的主要手段。在减数分裂中，HR是染色体基因交换过程中的主要参与者之一，对生物体的繁衍和基因多样性有着极其重要的意义；另外，HR参与非程序性的DNA损伤则对维持染色体基因稳定性以及阻止导致包括癌症在内的诸多疾病的基因变异有至关重要的意义。HR的机制虽然被广泛的研究，但尚未全面彻底地理清，尤其是在DNA同源匹配的机制方面，更是需要通过进一步的研究来阐明。本申请人在国外一直从事 HR的研究，在DNA同源匹配方面做了一些基础的工作，希望能够通过本项目的研究，进一步弄清和阐释DNA同源匹配的机制。为靶向于基因修复的癌症等疾病的治疗提供新的思路。