DNA replication

Before a cell can divide, it must first duplicate its DNA. This figure provides an overview of the DNA replication process. In the first step, a portion of the double helix (blue) is unwound by a helicase. Next, a molecule of DNA polymerase (green) binds to one strand of the DNA. It moves along the strand, using it as a template for assembling a leading strand (red) of nucleotides and reforming a double helix. Because DNA synthesis can only occur 5' to 3', a second DNA polymerase molecule (also green) is used to bind to the other template strand as the double helix opens. This molecule must synthesize discontinuous segments of polynucleotides (called Okazaki Fragments). Another enzyme, DNA Ligase (yellow), then stitches these together into the lagging strand.

The process of duplicating a cell's genome, required at each cell division. Replication, like all cellular activities, requires specialized proteins for carrying out the job. In the first step of replication, a special protein, called a helicase, unwinds a portion of the parental DNA double helix. Next, a molecule of DNA polymerase – a common name for two categories of enzymes that influence the synthesis of DNA – binds to one strand of the DNA. DNA polymerase begins to move along the DNA strand in the 3' to 5' direction, using the single-stranded DNA as a template. This newly synthesized strand is called the leading strand and is necessary for forming new nucleotides and reforming a double helix. Because DNA synthesis can only occur in the 5' to 3' direction, a second DNA polymerase molecule is used to bind to the other template strand as the double helix opens. This molecule synthesizes discontinuous segments of polynucleotides, called Okazaki fragments. Another enzyme, called DNA ligase, is responsible for stitching these fragments together into what is called the lagging strand.

The average human chromosome contains an enormous number of nucleotide pairs that are copied at about 50 base pairs per second. Yet, the entire replication process takes only about an hour. This is because there are many replication origin sites on a eukaryotic chromosome. Therefore, replication can begin at some origins earlier than at others. As replication nears completion, "bubbles" of newly replicated DNA meet and fuse, forming two new molecules.

With multiple replication origin sites, one might ask, how does the cell know which DNA has already been replicated and which still awaits replication? To date, two replication control mechanisms have been identified: one positive and one negative. For DNA to be replicated, each replication origin site must be bound by a set of proteins called the Origin Recognition Complex. These remain attached to the DNA throughout the replication process. Specific accessory proteins, called licensing factors, must also be present for initiation of replication. Destruction of these proteins after initiation of replication prevents further replication cycles from occurring. This is because licensing factors are only produced when the nuclear membrane of a cell breaks down during mitosis.

Related categories

• BIOCHEMISTRY
• GENETICS AND HEREDITY

Source: National Center for Biotechnology Information

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