STRUCTURAL ANALYSIS OF PROTEINS ASSOCIATED WITH REPLICATION INITIATION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 这项工作的目标是基于结构的理解如何启动DNA复制。复制起始于基因组上的多个位点，称为DNA复制起点。专门的蛋白质复合物在这些位点结合，并准备复制的双链体。这些集合体的活性受到严格控制，以确保每个细胞周期只产生一个基因组拷贝。这些大型复合物的结构、调节和作用机制尚不完全清楚。我们的工作具有实际意义，因为起源复合物的调节变化有助于人类癌症。对细菌复合物的研究将为开发新型抗生素提供急需的靶点。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this work is a structure-based understanding of how DNA replication is initiated. Replication initiates at multiple sites on the genome called origins of DNA replication. Specialized protein complexes bind at these sites and prepare the duplex for replication. The activity of these ensembles is tightly controlled to ensure that only one copy of the genome is made per cell cycle. The architecture, regulation and mechanisms of action of these large complexes are incompletely understood. Our work is of practical significance because regulatory changes in origin complexes contribute to human cancers. Efforts with bacterial complexes will provide much needed targets for development of novel antibiotics.