When scientists first began studying how DNA polymerase works during replication, they considered that it always added nucleotides in a continuous fashion. That is, they thought the enzyme always followed right behind the replication fork, laying down nucleotides as soon as the parent strands were exposed. But in the 1960s, a molecular biologist named Reiji Okazaki challenged that view. He and his colleagues had begun to think that the action of DNA polymerase was not always continuous. Their ideas stemmed from a combination of discoveries they’d made in the lab and a thorough knowledge of the structure of DNA. Thus, they came to know about the synthesis of leading and lagging strands.
Models of DNA synthesis often show it as occurring independently on the leading and lagging strands, with separate DNA Polymerase IIIs on each. However, replication at any one fork is under the control of a single, dimeric DNAPol III holoenzyme that replicates both parental DNA strands simultaneously. The process occurs consistent with the requirement that new strand synthesis always occurs 5′3′. At least 20 different enzymes and factors, including DNA helicases, DNA polymerases, RNA primases, DNA TOPOISOMERASES and DNA ligases are involved in the complex process of DNA replication.
During DNA replication, the replication of one of the two strands of DNA proceeds in a relatively straightforward manner. DNA polymerase adds nucleotides continuously, following directly behind the unzipping replication fork. However, the replication of the second strand is far more complex. Because the two strands of DNA are antiparallel, DNA polymerase must replicate them in opposite directions. Therefore, the replication of the second strand follows in a direction opposite the replication fork, and it does so discontinuously, replicating a segment of DNA at a time. The two strands of DNA are called leading- and lagging-strands, respectively. As DNA polymerase is moving away from helicase, it must constantly return to copy newly separated stretches of DNA. This means the lagging strand is copied as a series of short fragments (Okazaki fragments), each preceded by a primer.
The primers are replaced with DNA bases and the fragments joined together by a combination of DNA pol I and DNA ligase. The leading strand receives one RNA primer while the lagging strand receives many. The leading strand is continuously extended from the primer by a DNA polymerase with high processivity, while the lagging strand is extended discontinuously from each primer forming Okazaki fragments.
The first parent strand of DNA which runs in the 3′ to 5′ direction toward the fork, and it’s able to be replicated continuously by DNA polymerase. The other strand, called the lagging strand, is the parent strand which runs in the 5′ to 3′ direction toward the fork, and it’s replicated discontinuously.
Synthesis off the leading strand occurs in the 5′3′ direction, which is oriented towards the replication fork. To achieve the same orientation on the lagging strand, the lagging strand loops around the subunit. This allows either parental strands to enter the alternate subunits of the polymerase in the same 5′-3′ orientation as well as the same right-to-left direction. It also means that lagging strand synthesis will trail a series of Okazaki fragments as successive segments of the parental strand pass through the polymerase.