The DNA molecule forms the basis of all known life because its structure enables it to be easily copied within living cells, allowing them to reproduce. An organism’s genetic information is contained within its DNA, and accurate duplication is required to pass on this information to subsequent generations. The copying of genetic material within the cell nucleus is called DNA replication. The mechanism by which it occurs is known as semi-conservative replication, and it involves the molecule splitting into two parts, each of which forms a template for a complete new molecule. Materials available within the cell are then added to these templates to complete the process.
The Structure of DNA
Each DNA molecule is made up of two strands, consisting of sugar and phosphate groups, with molecules known as bases forming links between them. There are four different bases: adenine (A), guanine (G), cytosine (C) and thymine (T). Each base, along with the sugar and phosphate groups to which it is attached, is known as a nucleotide. The two strands are held together by hydrogen bonds between the bases; A bonds with T and C with G, so that they form pairs known as complementary base pairs.
The strands form a double helix, or two parallel spiral structures, while the base pairs span the gap between the strands. The DNA molecules are normally tightly coiled, many times over, and form structures known as chromosomes. The complete genetic information, or genome for an organism is contained within a set of chromosomes; the human genome contains about three billion base pairs. DNA replication forms a new set of chromosomes, prior to cell division. The replication process can be broken down into a number of stages, each controlled by enzymes.
To replicate, the DNA strands must be separated. The hydrogen bonds between the base pairs are strong enough to hold the strands together under normal circumstances, but weak enough to allow them to be pulled apart easily when required. Since the molecule is normally in a highly coiled state, the two strands will not split without some help. Enzymes called gyrases work to relax, or uncoil, the DNA, while enzymes called helicases begin to unzip it, breaking the hydrogen bonds between the base pairs. Special proteins then bind to the separated strands in order to keep them apart and allow replication to occur.
Nucleotides exist independently of DNA in the nucleus of a cell or, in the case of bacteria, within the cell fluid. When a DNA molecule has been split, these free nucleotides bond with the unpaired complementary bases of each strand — A to T and C to G — forming a new, double-stranded molecule. This process is enabled by enzymes known as DNA polymerases. The two resulting copies each have one new strand and one from the original molecule. This is why DNA replication is called semi-conservative — half of each molecule is new and half is saved from its parent.
The processes of splitting and duplication overlap. As strands come apart, new complementary strands are built while the split continues along the double helix. DNA molecules in most organisms are very long, so it is more efficient for the splitting and duplication to occur in many places at once. These points are known as origins of replication. When two such origins meet, enzymes called ligases join the new strands together.
The replication process is extremely accurate, but errors do occur. Sometimes, a bond can form between the wrong combination of bases. For example, G can occasionally bond with T instead of A. The bases can also exist in slightly different forms that can bond in other, incorrect, pairings.
Typically, there is around one error for every 100 million base pair bonds. In a human, this would result in about 30 errors for each complete replication. There are, however, a number of error checking and correction mechanisms that detect and repair mistakes very effectively. For example, bonds between mismatched base pairs are relatively unstable, and the polymerase enzymes that assist the duplication process can also detach an incorrect nucleotide, allowing a new, correct, one to be added. These reduce the average number of errors per replication to about three.
Replication Errors: Mutations, Cancer, and Evolution
Errors in DNA replication are usually a bad thing at the individual level. They can lead to mutations, which are generally unfavorable; they may result in cancer or other life-threatening diseases. On the other hand, without these errors, human beings and other organisms as they are known today would not be here. Occasionally, a mutation can give an advantage, increasing an organism’s chances of surviving long enough to reproduce and pass on the favorable change, which will then become more common. This is how evolution works: replication errors allow organisms to adapt to changing environments and to evolve into new life forms.