DNA Replication Fork, Bacterial

DNA replication, the basis for biological inheritance, is a fundamental process occurring in all living organisms requiring the complete genome to be copied before each cell division. In Escherichia coli, the single circular chromosome is 4.6×10⁶ base pairs (bp) in length and can be replicated in as little as 20 min. Replication of bacterial DNA is, thus, rapid. DNA replication must also be extremely accurate to avoid deleterious mutations in the genetic information. The error frequency during E. coli replication is estimated to be 10^?7, or one mismatch per 10⁷ bp replicated, before additional correction by the mismatch-repair system. Replication in E. coli is initiated at a specific DNA sequence by a series of reactions in which the DNA duplex is opened to allow the binding of the replication proteins. Replication is bidirectional with two replication forks moving in opposite directions. DNA synthesis at each fork is carried out by a complex of many proteins, known as a 'replisome'. It includes the leading- and lagging-strand DNA polymerases that synthesize the daughter DNA strands, and their associated clamps and clamp loader, collectively known as the 'holoenzyme'. The replisome also contains a primosome consisting of a primase to make short RNA chains to initiate new DNA fragments on the lagging strand, a helicase to unwind the parental duplex, and a helicase-loading protein. Single-stranded DNA-binding protein coats the lagging strand before it is replicated. Synthesis of the leading and lagging strand is a highly coordinated process.