DNA replication

DNA replication is how a cell creates precise copies of its DNA, a process found in all living things and vital for passing on genetic information, dividing cells, and mending damaged tissue. It guarantees that after cell division, each daughter cell gets a complete set of DNA molecules.

DNA usually exists as a double-stranded molecule, with two complementary strands held together by base pairing between their nucleotides. These two linear strands are twisted into a double helix shape. During replication, the strands separate, and each original strand acts as a template to build a new complementary partner strand—this is called semiconservative replication. The result is that every new DNA molecule contains one original strand and one freshly made strand. Cells have proofreading and error-checking systems that ensure replication happens with very high accuracy.

Replication typically starts at specific spots called origins of replication, which are spread throughout the genome. Enzymes called helicases unwind the DNA at these origins, creating replication forks that move in both directions. Many proteins gather at the replication fork to start and continue DNA synthesis. The key enzyme, DNA polymerase, builds new strands by adding nucleotides that match the template strand. This replication takes place during the S phase of interphase.

DNA replication can also be done artificially, outside a cell. Scientists use DNA polymerases taken from cells along with artificial DNA primers to start synthesis at known sequences on a template. Common examples include polymerase chain reaction (PCR), ligase chain reaction (LCR), and transcription-mediated amplification (TMA). In March 2021, researchers found evidence suggesting that an early form of transfer RNA—a molecule needed for protein synthesis—might have acted as a replicator during the very first stages of life's origin.

**DNA structure**

DNA has a double-stranded structure, with both strands coiled into a double helix. Each single strand is a chain of four types of nucleotides. These nucleotides contain a deoxyribose sugar, a phosphate group, and a nucleobase. The four nucleobases are adenine, cytosine, guanine, and thymine (abbreviated A, C, G, T). Adenine and guanine are purines; cytosine and thymine are pyrimidines. Nucleotides link via phosphodiester bonds, forming a sugar-phosphate backbone with the bases pointing inward toward the opposite strand. Complementary bases pair through hydrogen bonds: adenine pairs with thymine (two hydrogen bonds), and guanine pairs with cytosine (three hydrogen bonds).

DNA strands have directionality, with ends called the 3′ (three-prime) and 5′ (five-prime) ends. By convention, when writing a sequence, the left end is the 5′ end and the right end is the 3′ end. The two strands of the double helix run in opposite directions—one goes 5′ to 3′, the other 3′ to 5′. These terms refer to carbon atom numbering on the deoxyribose sugar, indicating which carbon the next phosphate attaches to. This directionality matters because DNA polymerase can only add nucleotides to the 3′ end of a growing strand, so it synthesizes DNA in one direction only.

Because bases pair specifically, the information in each strand is redundant. Phosphodiester bonds (within a strand) are stronger than hydrogen bonds (between strands). Phosphodiester bonds connect the 5′ carbon of one nucleotide to the 3′ carbon of the next, while hydrogen bonds stabilize the double helix across its axis but not along its length. This allows the strands to be pulled apart. The nucleotides on a single strand can then be used as a template to rebuild a new partner strand.

**DNA polymerase**

DNA polymerases are a family of enzymes that handle all DNA replication. They cannot start a new strand from scratch—they can only extend an existing DNA or RNA strand that is paired with a template. To begin, a short RNA fragment called a primer must be made and paired with the template.

DNA polymerase adds new nucleotides one at a time to the 3′ end of the existing chain, matching each to the template strand by forming phosphodiester bonds. The energy for this comes from breaking the high-energy phosphate bonds in the free nucleotide triphosphates. Free bases with a sugar (deoxyribose for DNA) are called nucleosides; adding one or more phosphate groups makes them nucleotides. Nucleosides with three phosphates are nucleoside triphosphates. When a free nucleotide is added to the growing strand, a phosphodiester bond forms between its innermost phosphate and the deoxyribose of the last nucleotide in the chain.