rolling circle model of dna replication

• Initiation of Replication

  • The process begins when an initiator protein binds to the origin of replication on the circular DNA molecule.

  • This protein introduces a single-strand nick at a specific site, creating a 3′ hydroxyl group and a 5′ phosphate group.

  • The 3′ end serves as a primer for DNA synthesis, while the 5′ end is displaced and remains bound to the initiator protein.

• Elongation of the Leading Strand

  • DNA polymerase III attaches to the 3′ end of the nicked strand and begins synthesizing the new DNA strand in the 5′ to 3′ direction.

  • The original, uncut strand acts as the template for this continuous synthesis.

  • As replication progresses, the newly synthesized strand displaces the original strand, forming a single-stranded DNA (ssDNA) molecule.

• Formation of Concatemers

  • The continuous replication around the circular DNA template results in the production of concatemeric DNA.

  • A concatemer is a long, linear DNA molecule consisting of multiple linked copies of the original genome.

  • These concatemers can be several kilobases in length and are often cleaved into unit-length genomes for packaging into new virions.​

• Termination and Circularization

  • Replication continues until a termination signal is encountered, at which point the initiator protein makes another nick to release the newly synthesized strand.

  • The free 3′ end of the released strand serves as a primer for the synthesis of a complementary strand, converting the ssDNA into double-stranded DNA (dsDNA).

  • DNA polymerase I removes any RNA primers, replacing them with DNA nucleotides, and DNA ligase seals the nicks, resulting in a complete circular dsDNA molecule.

Check this note – 

Rolling Circle Replication –  Mechanism, Application