How DNA Makes Copies of Itself
Steven Kuensting (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons for the DNA replication animation.
Before a cell divides, its DNA must be replicated (duplicated). Because the two strands of a DNA molecule have complementary base pairs, the nucleotide sequence of each strand automatically supplies the information needed to produce its new partner. The two strands of a DNA molecule are separated and each is used as a pattern or template to produce a complementary strand. Each template and its new complement together then form a new DNA double helix, identical to the original. Because the two new DNA molecules each contain a new strand of nucleotides along with one strand from the parent molecule, we say that the process of DNA replication is semi-conservative.
Before replication can occur, the length of the DNA double helix about to be copied must be unwound. Once the DNA strands have been unwound, they must be unzipped to expose the bases so that new nucleotide partners can bond to them. These tasks are accomplished by the enzyme helicase—one of many proteins that work as a micro-tools inside the cell. In the animation to the left, helicase is represented by the small key to symbolize unlocking the molecule.
Another enzyme DNA polymerase then moves along the exposed DNA strand joining newly arrived nucleotides into a new DNA strand that is complementary to the template. DNA polymerase is represented by the small brown pastebrush in the animation.
DNA polymerase makes very few errors and it corrects most of those quickly. In addition, there are other enzymes that follow along and "proofread" the nucleotides to be certain that the new nucleotides are actually complementary to the template strand. Any misfits are booted out and replaced with the proper base. Thanks to this magnificent system, DNA is consistently replicated with less than one mistake per billion nucleotides! The green rectangle with the pointed side represents a proofreader enzyme. Notice as it travels down the newly formed nucleotide chain, it encounters several places that have not been completely bonded. At that point, the "enzyme" turns red and a proper bond is formed.
Each cell contains a family of more than thirty enzymes necessary to insure the accurate replication of DNA.
Not represented in the animation are the primers necessary for DNA replication. Though DNA polymerase can elongate a polynucleotide strand by adding new nucleotides, it cannot start a strand from scratch because it can only bond new nucleotides to a free sugar (3') end of a nucleotide chain. DNA polymerase requires the assistance of a primer, a previously existing short strand of DNA (or RNA) that is complementary to the first part of the DNA segment being copied. This small strand of nucleotides anneals (binds) by complementary base pairing to the beginning of the area being copied. With the primer in place, DNA polymerase is then able to continue adding the rest of the pairs of the segment until a new double strand of DNA is completed. Primers are formed from free nucleotides in the cell by enzymes called DNA primases.
Replication occurs differently on the antiparallel strands of DNA. That nucleotides can be added only to the sugar or 3' end of the growing complementary chain presents no problem for the side of the DNA chain opening at its phosphate or 5' end. The primer that binds to the first few exposed bases will end with a sugar (3') where the phosphate of a new nucleotide can be attached. From there on, DNA polymerase can continuously synthesize the growing complementary strand. This strand of DNA is called the leading strand.
A different challenge faces DNA polymerase when the complementary side of the DNA molecule begins unzipping from its sugar (3') toward its phosphate (5') end. A primer of complementary molecules attaching to the opening end of this chain would have a phosphate not a sugar at its exposed end so that new nucleotides could not be joined. To get around this problem, this strand is synthesized in small pieces backward from the overall direction of replication. This strand is called the lagging strand. The short segments of newly assembled DNA from which the lagging strand is built are called Okazaki fragments. As replication proceeds and nucleotides are added to the 3' end of the Okazaki fragments, they come to meet each other. The primer fragments are then booted out by enzymes and replaced by appropriate DNA nucleotides. The whole thing is then stitched together by another enzyme called DNA ligase.
This little animation in the upper left provides a nice overview of the process of DNA replication. However, it does not approach representing the complexity of DNA replication. I strongly recommend watching the attached videos if you are preparing for an exam in an advanced high school or college class. Thank you to Steven Kuensting for sharing his work on Wikimedia Commons.