The central dogma of molecular biology explains the flow of genetic information in the cell between between information-carrying biopolymers (DNA, RNA and protein). It states that the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible.
{#fig:central_dogma}
The genetic code of an organism is stored in DNA, which is converted into portable RNA messages in a process called transcription. These messages travel from the cell nucleus (where the DNA resides) to the ribosomes where they are used as template to make specific proteins in a process called translation. The central dogma states that the pattern of information that occurs most frequently in our cells is:
- From existing DNA to make new DNA (replication)
- From DNA to make new RNA (transcription)
- From RNA to make new proteins (translation).
Besides these, there are some notable possibilities. For instance, retroviruses are able to generate DNA from RNA via reverse-transcription, and some viruses use RNA to make protein. All this is shown in @fig:central_dogma. The generated proteins carry out most of the cellular functions such as metabolism, DNA regulation, and replication.
The DNA molecule stores the genetic information of an organism. DNA contains regions called genes, which encode for the proteins that carry out most of the cellular function. Other regions of the DNA contain regulatory elements, which partially influence the level of expression of each gene.
The DNA molecule consists of two strands that wind around to form a shape known as a double helix. Each strand has a backbone made of alternating sugar (deoxyribose) and phosphate groups. Attached to each sugar is one of the four bases: adenine, cytosine, guanine, and thymine, frequently represented using the letters A, C, G, and T respectively. The two strands are held together by bonds between the bases: A and T are connected by two hydrogen bonds, while C and G are connected by three bonds. This specificity in pairing means that one strand can be used as a template to generate the other strand.
The DNA strands also have directionality, which refers to the positions of the pentose ring where the phosphate backbone connects. This directionality convention comes from the fact that DNA and RNA polymerase synthesize in the 5' to 3' direction. The complementary pairing with directionality means that the DNA strands are anti-parallel. In other words the 5' end of one strand is adjacent to the 3' end of the other strand. As a result, DNA can be read both in the 3' to 5' direction and the 5' to 3' direction, and genes and other functional elements can be found in each direction (on either strand). By convention, DNA is written from 5' to 3'.
Base pairing between nucleotides of DNA constitutes its primary and secondary structure. In addition to DNA’s secondary structure, there are several extra levels of structure that allow DNA to be tightly compacted and influence gene expression. The tertiary structure describes the twist in the DNA ladder that forms a helical shape. In the quaternary structure, DNA is tightly wound around small proteins called histones. These DNA-histone complexes are further wound into tighter structures seen in chromatin.
The structure of DNA with its weak hydrogen bonds between the bases in the center allows the strands to easily be separated for the purpose of DNA replication. In the replication of DNA, the two complementary strands are separated, and each of the strands are used as templates for the construction of a new strand. DNA polymerases attach to each of the strands at the origin of replication, reading each existing strand from the 3' to 5' direction and placing complementary bases such that the new strand grows in the 5' to 3' direction. Because the new strand must grow from 5' to 3', one strand (leading strand) can be copied continuously, while the other (lagging strand) grows in fragments that are later pasted together by DNA ligase. The end result is 2 double-stranded pieces of DNA, where each is composed of 1 old strand, and 1 new strand. For this reason, DNA replication is semi-conservative.
Transcription is the process to produce RNA using a DNA template. The DNA is partially unwound to form a bubble, and RNA polymerase is recruited to the transcription start site (TSS) by regulatory protein complexes. RNA polymerase reads the DNA from the 3’ to 5’ direction and placing down complementary bases to form messenger RNA (mRNA). RNA uses the same nucleotides as DNA, except Uracil (U) is used instead of Thymine (T).
Messenger RNA (mRNA) in eukaryotes experience post-translational modifications, or processes that edit the mRNA strand further. Most notably, a process called splicing removes introns (intervening regions which don’t code for protein), so that only the coding regions (the exons), remain. Different regions of the primary transcript may be spliced out and each can lead to a different protein product. This phenomenon is referred to as alternative splicing. In this way, an large number of protein products can be generated based on different splicing permutations. In addition to splicing, both ends of the mRNA molecule are processed. The 5’ end is capped with a modified guanine nucleotide. At the 3’ end, roughly 250 adenine residues are added to form a poly(A) tail.