DNA Replication Termination in Escherichia coli.

描述(申请人提供)：准确完成染色体复制的过程还不是很清楚。为了在复制过程中保持基因组的完整性，细胞必须有能力识别复制区域，限制正在进行的复制分叉，并在不获得或丢失核苷酸的情况下加入收敛的子链。这一过程很可能是调控所有细胞中准确的基因组复制的基本步骤，并且必须以非凡的效率发生。如果不能准确地完成复制，将对细胞造成灾难性的后果，产生过度复制或复制不足的基因组区域，并导致基因组稳定性的丧失，而基因组稳定性是大多数可遗传和散发性癌症的细胞进展的主要因素。 大肠杆菌recBC和recD的突变已被证明会使细胞在质粒和噬菌体上完成复制的能力丧失，一些证据表明，它们在染色体上也可能起到类似的作用。这项研究的目标是描述染色体复制的最后步骤，并确定recBC和recD在这一过程中的作用。这些实验是必要的，以表征这一关键的，但迄今未被检验的，准确的染色体复制机制。

DESCRIPTION (provided by applicant): The process by which chromosomal replication is accurately completed is not well understood. To maintain genomic integrity during replication, cells must have an ability to recognize replicated regions, limit ongoing replication forks, and join converging daughter strands without gaining or losing a nucleotide. This process is likely to be a fundamental step in regulating accurate genomic duplication in all cells and must occur with remarkable efficiency. Failure to complete replication precisely would have disastrous consequences for the cell, producing genomic regions that are overreplicated or underreplicated, and leading to a loss in genomic stability, which is a primary factor in the cellular progression of most heritable and sporadic forms of cancer. Mutations in E. coli recBC and recD have been shown to inactivate the cell's ability to complete replication on plasmids and bacteriophage, and some evidence suggests that they may function similarly on the chromosome as well. The goal of this research project is to characterize the final steps of chromosomal replication and to define the roles of recBC and recD in this process. These experiments are necessary to characterize this critical, yet heretofore unexamined, mechanism for accurate chromosomal replication.