DNA Replication
Each strand in a parent duplex DNA acts as a template for synthesis of a daughter strand and remains base-
Replication begins at a sequence called an origin. Each eukaryotic chromosomal DNA molecule contains multiple replication origins.
DNA polymerases, unlike RNA polymerases, cannot unwind the strands of duplex DNA and cannot initiate synthesis of new strands complementary to the template strands.
At a replication fork, one daughter strand (the leading strand) is elongated continuously. The other daughter strand (the lagging strand) is formed as a series of discontinuous Okazaki fragments from primers synthesized every 100 to 200 nucleotides (Figure 5-29).
The ribonucleotides at the 5′ end of each Okazaki fragment are removed and replaced by elongation of the 3′ end of the next Okazaki fragment. Finally, adjacent Okazaki fragments are joined by DNA ligase.
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Helicases use energy from ATP hydrolysis to separate the parent (template) DNA strands, which are initially bound by multiple copies of a single-
Most of the DNA in eukaryotic cells is synthesized by Pol δ and Pol ε, which take over from Pol α and continue elongation of the daughter strands in the 5′→3′ direction. Pol δ synthesizes most of the length of the lagging strand, while Pol ε synthesizes the leading strand. Pol δ and Pol ε remain stably associated with the template by binding to PCNA, a trimeric protein that encircles the daughter duplex DNA, functioning as a sliding clamp (see Figure 5-30).
DNA replication generally occurs by a bidirectional mechanism in which two replication forks form at an origin and move in opposite directions, and both template strands are copied at each fork (see Figure 5-32).
MCM helicases initiate eukaryotic DNA replication in vivo at multiple origins spaced along chromosomal DNA. Synthesis of eukaryotic DNA is regulated by controls on the binding and activity of these helicases