The separation of the two template strands and the synthesis of new daughter DNA molecules creates a moving "replication fork" (Figure 2), in which base pairs nucleotides (either DNA or RNA) linked by weak bonds
Inhibitors of viral helicase-primase enzymes are being tested as a new treatment for herpes virus infection.
Figure 2. Model of a bacterial replication fork.
ATP adenosine triphosphate, a high-energy compound used to power cell processes double-stranded DNA is continually unwound and copied. The unwinding of DNA poses special problems, which can be visualized by imagining pulling apart two pieces of string that are tightly wound around each other. The pulling apart requires energy; the strands tend to rewind if not held apart; and the region ahead of the separated strands becomes even more tightly twisted.
Proteins at the replication fork address each of these problems. DNA polymerases are not able to unwind double-stranded DNA, which requires energy to break the hydrogen bonds between the bases that hold the strands together. This task is accomplished by the enzyme DNA helicase, which uses the energy in ATP to unwind the template DNA at the replication fork. The single strands are then bound by a single-strand binding protein (called SSB in bacteria and RPA in eukaryotes), which prevents the strands from reassociating to form double-stranded DNA. Unwinding the DNA at the replication fork causes the DNA ahead of the fork to rotate and become twisted on itself. To prevent this from happening, an enzyme called DNA gyrase (in bacteria) or topoisomerase (in eukaryotes) moves ahead of the
LEADING AND LAGGING STRAND SYNTHESIS
Lagging strand synthesis
> 5' parental strand
DNA primase copies primer
DNA polymerase elongates primers
DNA polymerase removes primer and fills gap
DNA ligase joins fragments
Figure 3. Leading and lagging strand synthesis. Adapted from Lodish, 1999.
replication fork, breaking, swiveling, and rejoining the double helix to relieve the strain.
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