Helicases at the replication fork.

Helicases are fundamental components of all replication complexes since unwinding of the double-stranded template to generate single-stranded DNA is essential to direct DNA synthesis by polymerases. However, helicases are also required in many other steps of DNA replication. Replicative helicases not only unwind the template DNA but also play key roles in regulating priming of DNA synthesis and coordination of leading and lagging strand DNA polymerases. Accessory helicases also aid replicative helicases in unwinding of the template strands in the presence of proteins bound to the DNA, minimising the risks posed by nucleoprotein complexes to continued fork movement. Helicases also play critical roles in Okazaki fragment processing in eukaryotes and may also be needed to minimise topological problems when replication forks converge. Thus fork movement, coordination of DNA synthesis, lagging strand maturation and termination of replication all depend on helicases. Moreover, if disaster strikes and a replication fork breaks down then reloading of the replication machinery is effected by helicases, at least in bacteria. This chapter describes how helicases function in these multiple steps at the fork and how DNA unwinding is coordinated with other catalytic processes to ensure efficient, high fidelity duplication of the genetic material in all organisms.