MECHANISM OF TERMINATION OF DNA REPLICATION

DNA复制调控机制的研究及其对细胞增殖的影响 与细胞分裂的协调对于增殖 例如癌症。 我很重要，但不完全理解这一步 更大的问题是复制终止的机制和控制， 以及它与细胞分裂的可能联系。 利用E. coli和B. 枯草杆菌和耐药质粒R6 K作为模型系统，我们提出 研究终止子的作用和调节机制， proteins. 具体地说，我们建议研究分子基础 的极性的反解旋酶活性的ter蛋白质， 结合了遗传学和生物化学的方法。 我们最近发现，ter蛋白的活性是 通过特异性蛋白质-蛋白质相互作用与一种新的 抗终止子蛋白 我们建议通过克隆，过度生产和提纯， 抗ter蛋白的同质性，并研究其生物化学和 其与ter蛋白相互作用的生理后果。 最后，我们结晶了B的ter β蛋白（RTP）。枯草杆菌， 晶体的分辨率为2.5A。 我们建议解决 不仅脱辅基蛋白的结构，而且蛋白质-DNA的结构 复杂.

The study of the mechanism of regulation of DNA replication and its coordination wit cell division is of obvious importance proliferation such as cancer. Am important, but incompletely understood step of this larger problem is the mechanism and control of replication terminating, and its possible link to cell division. Utilizing E. coli and B. subtilis and the drug resistance plasmid R6K as model systems, we propose to study the mechanism of action and regulation of the terminator proteins. Specifically, we propose to investigate the molecular basis of the polarity of the contrahelicase activities of ter proteins by combined genetic and biochemical approaches. We have recently discovered that the activity of the ter protein is modulated by specific protein-protein interaction with a novel antiterminator protein. We propose to clone, overproduce and purify to homogeneity the anti-ter protein, and to study the biochemistry and physiological consequences of its interaction with the ter protein. Finally, we have crystallized the ter beta protein (RTP) of B. subtilis, and the crystals diffract to a resolution of 2.5A. We propose to solve not only the structure of the apoprotein but also that of the protein-DNA complex.