DNA replication

DNA replication is the process by which a cell makes exact copies of its DNA. This process occurs in all organisms and is essential to biological inheritance, cell division, and repair of damaged tissues. DNA replication ensures that each of the newly divided daughter cells receives its own copy of each DNA molecule.

DNA most commonly occurs in double-stranded form, made up of two complementary strands held together by base pairing of the nucleotides comprising each strand. The two linear strands of a double-stranded DNA molecule typically twist together in the shape of a double helix. During replication, the two strands are separated, and each strand of the original DNA molecule then serves as a template for the production of a complementary counterpart strand, a process referred to as semiconservative replication. As a result, each replicated DNA molecule is composed of one original DNA strand as well as one newly synthesized strand. Cellular proofreading and error-checking mechanisms ensure near-perfect fidelity for DNA replication.

DNA replication usually begins at specific locations known as origins of replication which are scattered across the genome. Unwinding of DNA at the origin is accommodated by enzymes known as helicases and results in replication forks growing bi-directionally from the origin. Numerous proteins are associated with the replication fork to help in the initiation and continuation of DNA synthesis. Most prominently, DNA polymerase synthesizes the new strands by incorporating nucleotides that complement the nucleotides of the template strand. DNA replication occurs during the S (synthesis) stage of interphase.

DNA replication can also be performed in vitro (artificially, outside a cell). DNA polymerases isolated from cells and artificial DNA primers can be used to start DNA synthesis at known sequences in a template DNA molecule. Polymerase chain reaction (PCR), ligase chain reaction (LCR), and transcription-mediated amplification (TMA) are all common examples of this technique. In March 2021, researchers reported evidence suggesting that a preliminary form of transfer RNA, a necessary component of translation (the biological synthesis of new proteins in accordance with the genetic code), could have been a replicator molecule itself in the early abiogenesis of primordial life.

DNA is a double-stranded structure, with both strands coiled together to form the characteristic double helix. Each single strand of DNA is a chain of four types of nucleotides. Nucleotides in DNA contain a deoxyribose sugar, a phosphate, and a nucleobase. The four types of nucleotide correspond to the four nucleobases: adenine, cytosine, guanine, and thymine, commonly abbreviated as A, C, G, and T, respectively. Adenine and guanine are purine nucleobases, while cytosine and thymine are pyrimidines. These nucleotides form phosphodiester bonds, creating phosphate-deoxyribose backbone of the DNA double helix with the nucleobases pointing inward (i.e., toward the opposing strand). Complementary nucleobases are matched between strands through hydrogen bonds to form base pairs. Adenine pairs with thymine (two hydrogen bonds), and guanine pairs with cytosine (three hydrogen bonds).

DNA strands have a directionality, and the different ends of a single strand are called the "3′ (three-prime) end" and the "5′ (five-prime) end". By convention, if the base sequence of a single strand of DNA is given, the left end of the sequence is the 5′ end, while the right end of the sequence is the 3′ end. The strands of the double helix are anti-parallel, with one being 5′ to 3′, and the opposite strand 3′ to 5′. These terms refer to the chemical convention of numbering the carbon atoms comprising the deoxyribose molecule and indicate the specific carbon atom to which the next phosphate in the chain attaches. Directionality has consequences in DNA synthesis, because DNA polymerase can synthesize DNA in only one direction by adding nucleotides to the 3′ end of a DNA strand.

The pairing of complementary bases in DNA (through hydrogen bonding) means that the information contained within each strand is redundant. Phosphodiester (intra-strand) bonds are stronger than hydrogen (inter-strand) bonds. The actual job of the phosphodiester bonds is to connect the 5' carbon atom of one nucleotide to the 3' carbon atom of another nucleotide, while the hydrogen bonds stabilize DNA double helices across the helix axis but not in the direction of the longitudinal axis. This makes it possible to separate the strands from one another. The nucleotides on a single strand can therefore be used to reconstruct nucleotides on a newly synthesized partner strand.

DNA polymerases are a family of enzymes that carry out all forms of DNA replication. DNA polymerases in general cannot initiate synthesis of new strands but can only extend an existing DNA or RNA strand paired with a template strand. To begin synthesis, a short fragment of RNA, called a primer, must be created and paired with the template DNA strand.