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Rolling Circle Model of Replication

 

Rolling Circlet Model of Replication
Gilbert and Dressler,1968; Eisen, Pareira da Silva and Jacob, 1968) is the current model for explaining replication in single stranded DNA viruses, e.g. ØX174, and the transfer of E.coli sex factor (plasmid). The φXl74 chromosome consists of a single stranded DNA ring (Positive Strand).

The chromosome first becomes double stranded by the synthesis of a negative strand. Synthesis is presumed to begin at a specific initiation point on the template ring. One strand of the parental duplex ring is now cut at a specific point by an endonuclease. This enzyme recognizes a particular sequence at this point. As a result of the cut ('nick') a linear strand with 3' and 5' ends is created.

The 3' end serves as a primer for the synthesis of a new DNA strand under the catalytic action of DNA polymerase. The unbroken strand is used as the template for this purpose, and a complementary strand is synthesized. Thus the parental molecule itself is used as a primer for initiating replication.

The 5' end of the broken strand becomes attached to the plasma membrane of the host bacterium. Such replicating phage DNA is commonly found associated with bacterial membranes. The unbroken parental strand rolls and unwinds as synthesis proceeds, leaving a 'tail' which is attached to the membrane.

New DNA is also synthesized in the tail region in discontinuous segments in the 5'à3' direction. This synthesis is presumably preceeded by the synthesis of an RNA primer under the catalytic action of RNA polymerase. The tail is cut off by a specific endonuclease into a unit length progeny rod.

The rod may undergo circularization to form a new circular molecule. During this process the gap is closed by a ligase. The newly formed circular molecules can in turn become new rolling circles. Genetic information is preserved in the single stranded template ring which remains circular and serves as an endless template. There is no swivelling problem or creation of torque in the rolling circle model.

As the strands unwind the 3’ end is free to rotate on the unbroken strand. The growing point itself thus serves as a swivel. Evidence for the rolling circle model has been obtained from the replication of several viruses (M13, P2, T4, λ), replication resulting in transfer of genetic material during mating of bacteria, and the special DNA synthesis during oogenesis in Xenopus.

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