DNA replication is a fundamental process in cell biology that ensures the faithful duplication of the entire genome during cell division. It occurs in the S phase of the cell cycle and involves the synthesis of a new DNA strand complementary to each of the original parental DNA strands. The process of DNA replication can be summarized in several key steps:
Initiation: DNA replication starts at specific sites on the DNA molecule known as origins of replication. In eukaryotic cells, multiple origins of replication exist along the chromosomes. The process begins with the binding of initiator proteins to these origins, forming a pre-replication complex.Unwinding: Once the pre-replication complex is formed, the DNA helix is unwound at the origin of replication by an enzyme called helicase. Helicase breaks the hydrogen bonds between the two DNA strands, creating a replication fork with two single-stranded templates.Priming: The single-stranded DNA templates are unable to serve as templates for the synthesis of new DNA strands directly. Therefore, a short RNA primer is synthesized by an enzyme called primase. The RNA primer provides the 3'-OH group necessary for DNA polymerase to start the synthesis of a new DNA strand.Elongation: The actual synthesis of the new DNA strands occurs during the elongation phase. DNA polymerase, specifically DNA polymerase III in prokaryotes and a group of DNA polymerases in eukaryotes, is responsible for the elongation. DNA polymerase adds nucleotides to the 3'-OH end of the growing DNA strand in a 5' to 3' direction.On the leading strand, DNA synthesis occurs continuously in the same direction as the replication fork movement. On the lagging strand, DNA synthesis occurs discontinuously in small fragments called Okazaki fragments. Each Okazaki fragment requires a new RNA primer, and DNA polymerase extends each fragment until it reaches the previously synthesized fragment. The RNA primers are later removed, and the gaps between fragments are sealed by another enzyme called DNA ligase.
Termination: DNA replication continues bidirectionally from the origin until it reaches specific termination sites on the DNA molecule. Termination involves the dissociation of the replication machinery and the completion of the replication process.The key enzymes involved in DNA replication are:
Helicase: Unwinds the DNA double helix by breaking hydrogen bonds between the two strands.Primase: Synthesizes short RNA primers on the single-stranded DNA templates to initiate DNA synthesis.DNA polymerase: Catalyzes the addition of nucleotides to the growing DNA strands, using the parental DNA strands as templates.DNA ligase: Seals the gaps between Okazaki fragments on the lagging strand, creating a continuous DNA strand.Topoisomerase: Relieves the torsional strain and supercoiling generated during DNA unwinding.These enzymes work together in a highly coordinated manner to ensure accurate and efficient DNA replication, preserving the genetic information during cell division and inheritance.
