Replication is semiconservative: DNA’s two nucleotide strands separate, and each serves as a template on which a new strand is synthesized.
In theta replication of DNA, the two nucleotide strands of a circular DNA molecule unwind, creating a replication bubble; within each replication bubble, DNA is normally synthesized on both strands and at both replication forks, producing two circular DNA molecules.
Rolling-circle replication is initiated by a break in one strand of circular DNA, which produces a 3′-OH group to which new nucleotides are added while the 5′ end of the broken strand is displaced from the circle.
Linear eukaryotic DNA contains many origins of replication. Unwinding and replication take place on both templates at both ends of the replication bubble until adjacent replicons meet, resulting in two linear DNA molecules.
All DNA synthesis is in the 5′→3′ direction. Because the two nucleotide strands of DNA are antiparallel, replication takes place continuously on one strand (the leading strand) and discontinuously on the other (the lagging strand).
Replication begins when an initiator protein binds to a replication origin and unwinds a short stretch of DNA to which DNA helicase attaches. DNA helicase unwinds the DNA at the replication fork, single-strand-binding proteins bind to single nucleotide strands to prevent secondary structures, and DNA gyrase (a topoisomerase) removes the strain ahead of the replication fork that is generated by unwinding.
During replication, primase synthesizes short primers of RNA nucleotides, providing a 3′-OH group to which DNA polymerase can add DNA nucleotides.
DNA polymerase adds new nucleotides to the 3 end of a growing polynucleotide strand. Bacteria have two DNA polymerases that have primary roles in replication: DNA polymerase III, which synthesizes new DNA on the leading and lagging strands, and DNA polymerase I, which removes and replaces primers.
DNA ligase seals the breaks that remain in the sugar–phosphate backbones when the RNA primers are replaced by DNA nucleotides.
Several mechanisms ensure the high rate of accuracy in replication, including precise nucleotide selection, proofreading, and mismatch repair.
Precise replication at multiple origins in eukaryotes is ensured by a licensing factor that must attach to an origin before replication can begin.
Eukaryotic nucleosomes are quickly assembled on new molecules of DNA; newly assembled nucleosomes consist of a random mixture of old and new histone proteins.
The ends of linear eukaryotic DNA molecules are replicated by the enzyme telomerase.
Homologous recombination takes place through breaks in nucleotide strands, alignment of homologous DNA segments, and rejoining of the strands. Homologous recombination requires a number of enzymes and proteins.
Gene conversion is nonreciprocal genetic exchange and produces abnormal ratios of gametes.