The leading strand is one of the two new DNA strands synthesized during DNA replication. It forms continuously as a single, uninterrupted piece, contrasting with the replication of its counterpart.
The DNA Replication Fork
Before DNA can be copied, the parental double helix must unwind and separate. Helicase initiates this process by breaking the hydrogen bonds holding the two strands together. This unwinding creates a Y-shaped structure called the replication fork, where DNA synthesis occurs. Single-strand binding proteins then attach to each exposed strand, stabilizing them and preventing rejoining.
DNA is antiparallel, meaning its two strands run in opposite directions. One strand runs 5′ to 3′, while its complementary partner runs 3′ to 5′. This structural characteristic influences how each new strand is synthesized, affecting both continuous and discontinuous replication at the fork.
Continuous Synthesis on the Leading Strand
The synthesis of new DNA is governed by a strict rule: DNA polymerase, the enzyme building the new DNA strand, can only add new nucleotides to the 3′ end of a growing strand. This means DNA synthesis always proceeds in a 5′ to 3′ direction relative to the new strand being built. For the leading strand, its template runs 3′ to 5′, allowing DNA polymerase to move in the same direction as the advancing replication fork.
To begin synthesis, primase lays down a short RNA primer. DNA Polymerase III then binds to this primer and adds deoxyribonucleotides continuously along the template strand. As helicase unwinds more DNA, DNA Polymerase III follows, extending the new leading strand towards the opening replication fork. This continuous synthesis makes leading strand replication straightforward.
Discontinuous Synthesis on the Lagging Strand
The lagging strand is synthesized discontinuously, in short segments. This is due to the antiparallel nature of the DNA template and the unidirectional activity of DNA polymerase. The lagging strand template runs 5′ to 3′, forcing DNA polymerase to synthesize the new strand away from the moving replication fork. As the replication fork opens, the polymerase must repeatedly start new fragments.
Okazaki fragments require their own RNA primer synthesized by primase. DNA Polymerase III then extends each primer, building a new DNA segment until it reaches the previous fragment’s primer. Subsequently, DNA Polymerase I removes these RNA primers and replaces them with DNA nucleotides. Finally, DNA ligase forms phosphodiester bonds, joining these individual Okazaki fragments into a single, continuous lagging strand.
The Major Enzymes of Replication
Numerous enzymes collaborate to ensure accurate and efficient DNA duplication. Each performs a specific function, contributing to the coordinated process of replication. Understanding their individual roles provides clarity.
Helicase unwinds the double-stranded DNA helix, breaking the hydrogen bonds between complementary base pairs and separating the two parental strands.
Primase synthesizes short RNA primers, which provide the necessary 3′-hydroxyl group for DNA polymerase to begin adding nucleotides.
DNA Polymerase III is the primary enzyme that synthesizes the bulk of the new DNA, extending the RNA primers by adding deoxyribonucleotides in the 5′ to 3′ direction on both leading and lagging strands.
DNA Polymerase I plays a distinct role in processing the lagging strand by removing the RNA primers and replacing them with DNA nucleotides. This enzyme also helps fill any small gaps that may arise during replication or repair.
Finally, DNA ligase is the molecular “glue,” forming phosphodiester bonds to join the Okazaki fragments on the lagging strand, thereby completing the synthesis of a continuous DNA molecule.