The entire process of rolling hairpin replication, which has distinct, sequential stages, can be summarized as follows:
*1. The coding portion of the genome is replicated, starting from the 3′-end of the 3′ hairpin, which acts as a primer, and continues until the newly synthesized strand is connected to the 5′-end of the 5′ hairpin, producing a duplex DNA molecule that has two strands of the coding portion of the genome.
*2. mRNA that encodes the viral replication initiator protein is transcribed and subsequently translated to synthesize the protein.
*3. The initiator protein binds to and cleaves the DNA within a region called the origin, which results in the hairpin unfolding into a linear, extended form. At the same time, the initiator protein establishes a replication fork with its helicase activity.
*4. The extended-form hairpin is replicated to create an inverted copy of the telomere on the newly synthesized strand.
*5. The two strands of that end refold back into two hairpins, which repositions the replication fork to switch templates and move in the opposite direction.
*6. DNA replication continues in a linear manner from one end to the other using the opposite strand as a template.
*7. Upon reaching the other end, that end's hairpin is unfolded and refolded to replicate the terminus and once again swap templates and change the direction of replication. This back-and-forth replication is continually repeated, producing a concatemer of multiple copies of the genome.
*8. The viral initiator protein periodically excises individual genomic strands of DNA from the replicative concatemer.
*9. Excised ssDNA genomes are packaged into newly constructed viral capsids.