spaced at intervals of approximately 100,000 base pairs (100 kilobase pairs, or 100 kb) along the length of the DNA. There are 6 billion base pairs in the human genome, located on forty-six chromosomes, and so each chromosome will have many origins of replication. Prokaryotic chromosomes typically have a single replication origin.
Replication origins are composed of special sequences of DNA that are recognized by replication initiator proteins, which bind to the origin sequences and then help to assemble other proteins required for DNA replication at these sites. The eukaryotic replication initiator protein is a complex containing six different subunits called the origin recognition complex (ORC). The bacterial replication initiator protein is called the dnaA protein. The timing of DNA replication is regulated by controlling the assembly of complexes at replication origins.
The distinct steps in the initiation of replication are understood better in bacteria than in eukaryotes, but several key steps are common to both. The first step is a change in the conformation of the initiator protein, which causes limited "melting" (that is, the separation of the two strands) of the double-stranded DNA next to the initiator binding site, thus exposing single-stranded regions of the template (Figure 1). Two more proteins, DNA helicase and DNA primase, then join the complex. Replication initiation is triggered by the activation of the helicase and primase, and the subsequent recruitment of DNA polymerase. In prokaryotes, the particular form of the enzyme is called DNA polymerase III. Other proteins are also recruited, each of whose functions are discussed below.
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