Dynamic coupling between the motors of DNA replication: hexameric helicase, DNA polymerase, and primase

Helicases are molecular motor proteins that couple NTP hydrolysis to directional movement along nucleic acids. A class of helicases characterized by their ring-shaped hexameric structures translocate processively and unidirectionally along single-stranded (ss) DNA to separate the strands of double-stranded (ds) DNA, aiding both in the initiation and fork progression during DNA replication. These replicative ring-shaped helicases are found from virus to human. We review recent biochemical and structural studies that have expanded our understanding on how hexameric helicases use the NTPase reaction to translocate on ssDNA, unwind dsDNA, and how their physical and functional interactions with the DNA polymerase and primase enzymes coordinate replication of the two strands of dsDNA.

► Recent nucleic acid bound structures of hexameric helicases reveal mechanism and polarity of translocation along ssDNA.
► Hexameric helicases unwind dsDNA by an active or a passive mechanism.
► Replicative helicases mediate physical and functional coupling with the DNA polymerase and primase enzymes.
► Ring shaped helicases modulate DNA synthesis and primer synthesis activities via dynamic coupling.