Nucleic acid

Nucleic acids are made ​​up of individual building blocks, the nucleotides macromolecules, built. Alternate simple sugars and phosphates form a chain, hangs a nucleobase at each sugar. Nucleic acids are in addition to proteins, carbohydrates and lipids, the fourth major group of biomolecules. Her most famous representative is deoxyribonucleic acid (DNA or DNA), the storage of genetic information. In addition to its role as information storage nucleic acids can also serve as signal transducers or catalyze biochemical reactions.

• 3.1 deoxyribonucleic acid (DNA, DNA)
• 3.2 ribonucleic acid (RNA, RNA)

History

Was first described in the nucleic acid of the Swiss physician Friedrich Miescher in 1869 after his studies in the laboratory - the former kitchen - the Tübingen castle. He was a member of the founder of Biochemistry, Felix Hoppe- Seyler. After Miescher his research on proteins gave up because they were too complex and diverse, he turned to the study of cell nuclei. Their function was completely unknown at that time. From the nuclei of white blood cells, he isolated a substance that significantly differed due to their high phosphorus content of proteins. He called it nuclein after the Latin word nucleus ( core). Although Miescher the function of nucleic came very close, he believed ultimately not that one substance could be responsible for the inheritance.

" If we (...) would accept that a single substance ( ... ) be the specific cause of fertilization in some way (...), so you would have no doubt mainly due to the nucleic think. "

Albrecht Kossel discovered that nuclein of four modules and sugar molecules is established. 1889, named Richard Altmann, who was first to nucleic acids in plant cells, the nucleic due to its chemical properties in nucleic acid to. Recognized until 1929 Phoebus Levene that the nucleic acid ( here, the deoxyribonucleic acid ) composed of deoxyribose, phosphoric acid groups and the four organic bases, adenine, guanine, cytosine and thymine. He coined the term ' nucleotide ' for these building blocks of nucleic acid. 1944 could prove Oswald Avery, Colin McLeod and Maclyn McCarty, that nucleic acids are the storage of genetic information and not - as previously thought - proteins.

The American James Watson ( b. 1928 ) and the British Francis Crick ( 1916-2004 ) and Maurice Wilkins ( 1916-2004 ) finally succeeded to elucidate the structure of deoxyribonucleic acid. In 1962, she received the Nobel Prize.

Frederick Sanger, Allan Maxam and Walter Gilbert developed in 1977 a method by which the order of the nucleotide building blocks, the sequence could be determined. This chain termination method is used today in automated methods to sequence DNA.

Construction

Chemical structure

Nucleic acids are chains of nucleotides as members. The central part of a nucleotide is the ring-shaped sugar molecule ( Pictured gray: the ribose). Numbered to the carbon atoms of the sugar clockwise from 1 to 5, so is C1 on a nucleobase ( Figure 1: red, green, yellow and blue) is attached via a glycosidic bond. C3 at a phosphate residue of the following nucleotide ( blue) is formed with the OH group of the sugar, an ester bond. On C5 of the sugar, a phosphate residue is bound via the other of the two phosphodiester bonds as well.

The phosphoric acid has ( potentially cleave three OH groups, protons ) three acid groups in an unbound state. In two of these three nucleic acid groups are esterified and thus can not release any more proton. For the acidic character, which gave its name to the nucleic acid, the third unbound acid function is responsible. It can act as a proton donor or is in the cell before deprotonated (negative charge on the oxygen atom). Under physiological conditions (pH 7), the nucleic acid due to this negatively charged oxygen atom in total a large anion. In the separation of nucleic acids according to their size can therefore use an electric field in which nucleic acids generally migrate to the anode (see agarose gel electrophoresis).

Orientation

Their structure gives the nucleic acid polarity orientation respectively in the chain block sequence. She has a 5 'end (pronounced 5 -prime end ) named after the C5 atom of the sugar to which a phosphate group is attached and a 3' end at which the free OH group at C3 of the chain terminates. Usually you write sequences, so Nukleotidfolgen, with the 5 'end beginning at the 3' end on. Organisms in the polarity is important. For example, there are DNA polymerases, the ' can build → 3' direction, and some correct improperly installed only nucleotides in the 3 ' one DNA strand only in 5 → 5' direction.

Spatial structure

The secondary structure is called the spatial orientation in nucleic acids. While the primary structure (sequence ) stores the information, determines the secondary structure of the size, durability, and also provides access to the stored information.

The simplest three-dimensional structure is of the double strand. Here, two nucleic acid chains are opposite in the opposite orientation. You are connected to each other via hydrogen bonds between the nucleobases. In this case, each pair with a purine base, a pyrimidine base, the nature of the respective pair determines the stability of the duplex. Between guanine and cytosine, three hydrogen bonds are formed, while adenine and thymine are connected by two hydrogen bonds (see Figure 2). The higher the GC content ( proportion of guanine - cytosine pairs ), the more stable the double strand and the more energy (heat) must be expended is to split it into single strands. A double strand may be comprised of two different nucleic acid molecules or of a single molecule. At the end of the double strand then forms a loop in the chain ' reversed ' so that the opposite orientation arises.

Wherein the double-stranded DNA as a result of overcoming the many bond angles around its own axis to form a double helix. There are both left - and right-handed helices. This to yourself meandering double strand can then further twisted and wrap around other structures such as histones (special proteins). The purpose of this further entanglement is the saving of space. Untwisted and stretched out the DNA of a single human chromosome would be about 4 cm long.

Natural nucleic acids

Nucleic acids are present in all living organisms. Your task is, among others, the genetic information, store the blueprint of the organism to exchange with others of their kind and bequeath to future generations. In all organisms that does the DNA. Only a few viruses ( retroviruses such as HIV ) use the less stable RNA as a storage medium.

Deoxyribonucleic acid (DNA, DNA)

DNA has as constituent sugar deoxyribose (hence the name deoxyribonucleic acid), which only differs from the ribose by the absence of OH group at the C2 atom. The reduction of the OH group to the simple H takes place only at the end of the nucleotide. So deoxyribonucleotides are formed from the ribonucleotides, the RNA building blocks. The difference, however, makes DNA much more chemically stable than RNA ( see Section justification RNA) and indeed so stable that they in sea water (1 ppb) and estuaries is solved to demonstrate ( to 44 ppb). In DNA the nucleobases adenine, cytosine, guanine and thymine are present, the latter being specific for DNA. Despite the small amount of four different basic modules much information can be stored.

DNA exists as double-stranded, which is wound upon itself forming a double helix. From the location identified by X-ray crystallography the three helix types, only the B-DNA has been demonstrated in vivo. She is a right-handed helix with a pitch ( length of the helix for a complete turn ) of 3.54 nm and 10 base pairs and a diameter of 2.37 nm Furthermore, there are the wider A- helix ( pitch of 2.53 nm, diameter 2, 55 nm) and the more stretched Z -helix ( pitch of 4.56 nm, diameter 1.84 nm). To an encoded in the DNA or the DNA gene read doubled even in the course of cell division, the helix is placed on a portion unwound by enzymes ( topoisomerase ) and the double strand in single strands of cleaved ( helicase ).

In bacteria, the DNA molecule is present as a ring-shaped, while the free ends, called telomeres has in eukaryotes. The nature of the DNA replication mechanism means that linear DNA molecules per doubling can be reduced by a few base pairs. The more often a cell divides, the shorter the DNA. The remains at limited cell division without consequences, because at the end of such a string are short sequences that are repeated several thousand times. So it's not lost genetic information. To some extent, the shortening compensated by the enzyme telomerase ( Only in stem cells and cancer cells). Falls below the length of the repetitive sequences at the end of the strand a certain length, then the cell no longer divides. This is one of the reasons for a limited life. Since bacteria have a circular DNA molecule, it does not come to a shortening of the strand with them.

Ribonucleic acid (RNA, RNA)

As already indicated in the upper portion, the OH group at the C2 atom of the ribose is responsible for the lower stability of the RNA. Indeed, she can, as well as the OH group at C3 for the normal chain formation, take a shortcut to the phosphate moiety. If there spontaneously to such transesterification, the nucleic acid chain is broken.

Another difference is that use is made in the DNA thymine, while present in the RNA uracil. Oxidative conditions or other factors can be chemically modified nucleobases within the DNA. So it happens occasionally to deamination ( removal of an NH2 group, instead it creates a = O group). In a double-strand then the sites for hydrogen bonding the opposite nucleobases do not fit together and there is a partial decomposition. Enzymes can cut and replace or repair modified nucleobases. As a template, they are geared to the second non-modified nucleobase. Does it now at cytosine deamination to such as uracil arises. Would uracil also commonly occur in the DNA, an enzyme could now no longer distinguish whether the uracil nucleobase is the wrong or the opposite guanine ( previously paired with cytosine ). In this case, important information may be changed, a mutation may occur. To avoid this confusion, but no uracil thymine is used in DNA in principle, uracil is recognized and removed from the DNA by specific enzymes uracil glycosylases. This can properly recognize and it is clear that each uracil in DNA is a broken cytosine enzymes by its additional methyl group. In RNA, the danger of the information revolution is not serious, since information is stored only in the short term and not only to an RNA molecule of each variety, but are hundreds available. Should some of them be broken, so that has no serious effects on the whole organism, as there are enough replacement.

Synthetic nucleic acids

A non-naturally occurring nucleic acid of interest for biotechnology is the peptide nucleic acid ( PNA abbreviated, from the English Peptide Nucleic Acid ).

In addition, numerous nucleic acid variants have been developed, the components of which are recognizable at first glance no more than ribo- (in the case of RNA) or deoxyribonucleotides (in the case of DNA):

• Phosphorothioate deoxyribonucleic acid
• Cyclohexene nucleic acids ( CeNA )
• N3 '→ P5' phosphoramidates (NP )
• Bridged nucleic acid ( engl. locked nucleic acid, LNA)
• Tricyclo deoxyribonucleic acids ( tcDNA )
• Morpholino - phosphoramidates ( MF)