DNA Replication Termination in Escherichia coli.

描述（由申请人提供）：染色体复制准确完成的过程尚不清楚。为了在复制过程中保持基因组的完整性，细胞必须能够识别复制区域，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连接聚合子链。这个过程很可能是调节所有细胞中精确的基因组复制的一个基本步骤，并且必须以显著的效率发生。不能精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，这是大多数遗传性和散发性癌症的细胞进展的主要因素。

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.