ABSTRACT
The duplication of genomic DNA is a necessary property of all growing cells. The basic mechanisms of DNA replication are similar in both prokaryotes and eukaryotes; the latter have evolved increasingly more complex and defined systems. The simplicity of the prokaryotic system and the complexity of the eukaryotic systems notwithstanding, the questions addressed regarding DNA duplication are essentially the same. How does replication begin? What are the recognition signals for the initiation of replication and the propagation of replication along the chromosome? What are the proteins that are involved in DNA replication? What are the detailed steps in the replication of DNA? What are the mechanisms that ensure fidelity of replication? While many of these questions have been answered using bacteriophages, viruses and bacteria,1'2 attempts are also being made to understand the replication of eukaryotic DNA based on the model developed for prokaryotic systems.3 Replication of DNA, in general, usually starts at a particular site in the genome (origin), and DNA synthesis proceeds bidirectionally away from an origin via two growing forks expanding in opposite directions. DNA synthesis at the growing fork is semiconservative and proceeds until both DNA strands of the chromosomes have been synthesized. The events leading to the initiation of DNA synthesis are not well understood, even though specific sites of initiation have been identified in viruses, bacteria, yeasts, and higher eukaryotes. On the other hand, events at the already growing fork are well understood in the bacterial system. In fact, the entire system for the synthesis of the growing fork has been reconstructed using purified proteins from bacteria. There are about 10 to 20 proteins involved at the growing fork in a multi-enzyme complex referred to as a replisome (see Chapter 2). However, once the duplication of chromosomal DNA has taken place, the process of termination of replication is again not well defined.
