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  Section: General Biochemistry » Nucleic Acid Synthesis
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DNA Replication and its Regulation

Content of Nucleic Acid Synthesis
» Nucleic Acids
» Structure and Function of Nucleic Acids
    » Basic Chemical Structure
    » Base Pairing in Nucleic Acids: Double Helical Structure of Dna
    » Size, Structure, Organization, and Complexity of Genomes
    » Information Storage, Processing, and Transfer
    » Chromosomal Dna Compaction and Its Implications in Replication and Transcription
    » DNA Sequence and Chromosome Organization
    » Repetitive Sequences: Selfish DNA
    » Chromatin Remodeling and Histone Acetylation
» Nucleic Acid Syntheses
    » Similarity of DNA and RNA Synthesis
    » DNA Replication Vs Transcription: Enzymatic Processes
    » Multiplicity of DNA and RNA Polymerases
» DNA Replication and Its Regulation
    » DNA Replication
    » Regulation of DNA Replication
    » Regulation of Bacterial DNA Replication at the Level of Initiation
    » DNA Chain Elongation and Termination in Prokaryotes
    » General Features of Eukaryotic DNA Replication
    » Licensing of Eukaryotic Genome Replication
    » Fidelity of DNA Replication
    » Replication of Telomeres—The End Game
    » Telomere Shortening: Linkage Between Telomere Length and Limited Life Span
» Maintenance of Genome Integrity
» DNA Manipulations and their Applications
» Transcriptional Processes
    » Recognition of Prokaryotic Promoters and Role of S-Factors
    » Regulation of Transcription in Bacteria
    » Eukaryotic Transcription
    » RNA Splicing in Metazoans
    » Regulation of Transcription in Eukaryotes
    » Fidelity of Transcription (RNA Editing)
» Chemical Synthesis of Nucleic Acids (Oligonucleotides)
» Bibliography of Nucleic Acid Synthesis
A. DNA Replication
DNA replication is initiated at discrete sequences called origin (ori) of replication to which DNA polymerase and accessory proteins bind and copy both strands, as predicted by the semi-conservative replication model (Fig. 2B). In contrast to unidirectional RNA synthesis, DNAreplication in most genomes occurs bidirectionally (Fig. 2B). This results in both continuous and discontinuous synthesis of the same strand on two sides of the origin of replication. Some circular genomes, such as mitochondrial DNA, are replicated unidirectionally. In these cases, replication starting at the ori proceeds continuously in the 5´→3´ direction, followed by discontinuous synthesis of the complementary strand. Termination occurs at the same site as the ori after the circle is completely traversed. During replication of the mitochondrial genome, elongation of the continuous strand pauses at some distance from the ori, resulting in a bubble (Θ structure) structure named a D-(displacement) loop (Fig. 4A).

The single-stranded DNA genomes of certain small E. coli viruses (such as M13 and φX174) are replicated in the form of rolling circles in which unidirectional synthesis of one (virus genome) strand occurs by continuous displacement from the template (complementary strand; Fig. 4A). The initial duplex DNA (called the replicative form or RF) is the template for rolling circle synthesis and is formed first by replication of the single-stranded form. Such a single-stranded circular DNA template has been exploited in recombinant DNA techniques.

Small organisms (e.g., bacteria), as well as plasmids and many viruses, have only one ori sequence per cellular genome (4.7×106 nucleotide pairs in E. coli), which is often an uninterrupted DNA molecule (Figs. 4A and 4B). In complex organisms, with a much larger genome size (∼3×109 nucleotide pairs for mammals), which is divided into multiple discrete chromosomes, thousands of ori sequence are present (Fig. 4C), although not all of them may be active in all cells; this requires that replication be regulated and coordinated.

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