How wide is the DNA molecule

Deoxyribonucleic acids

Deoxyribonucleiacids, Cancel DNS and (mostly) DNA (English), highly polymeric chain molecules (biopolymers), which have the ability to duplicate identically and, due to the linear connection of 4 basic building blocks in a non-random order, are carriers of the genetic information (The only exceptions are the so-called RNA viruses and RNA phages [single-stranded RNA phages], whose genetic information is encoded in the form of the nucleotide sequence of RNA [ribonucleic acids]).
The basic building blocks in the DNA are almost exclusively the 4 standard 2´-deoxyribonucleoside monophosphate 2´-deoxyadenosine-5´-monophosphate (dAMP), 2´-deoxycytidine-5´-monophosphate (dCMP), 2'-deoxyguanosine-5'-monophosphate (dGMP) and 2´-deoxythymidine-5´-monophosphate (dTMP) which are connected by esterification of the 5'-phosphate group of each basic building block with the 3'-hydroxyl group of the respective neighboring monomer (with the formation of a deoxyribose-phosphate backbone) (see Fig. deoxyribonucleic acids I). Under physiological conditions, DNA is not in the acid form, but as a polyanion with a negative charge per nucleotide residue (nucleotides). The cations required for electroneutrality are both simple organic cations and sodium (Na+), Potassium (K+), Ammonium (NH4+), as well as amines (e.g. spermidine) and basic proteins (DNA-binding proteins, histones; protein-DNA interaction.). - Secondary structure: With the exception of the DNAs of certain bacteriophages, e.g. B. ΦX174, fd and M13, which are single-stranded (single-stranded DNA phages) or double-stranded only in the replication stage, DNA consists of 2 complementary, antiparallel chains (antiparallelism), the base pairings to one Double helix-Structure (see Fig.) Are united. The artificial transfer of double-stranded DNA to single-stranded DNA, e.g. B. with the help of alkali, acid, agents that break hydrogen bonds (urea and formamide), but especially by increasing the temperature, is called DNADenaturation (in the case of a temperature increase also as DNA-Melt;melting). Because of the stronger binding of the G≡C base pairs (3 hydrogen bonds) compared to A = T base pairs (2 hydrogen bonds), the denaturation of DNA with a high GC content (or a low AT content) requires more stringent conditions (higher temperatures, higher concentrations) of urea, etc.). In the meantime it is also possible to separate the two DNA strands at least over short areas by tensile forces, whereby an average of about 12 pN has to be used per base pair.
In the cell, DNA is only locally and temporarily, e.g. B. at the replication forks (replication), converted into the state of separate single strands. In addition to the J.D. Watson and F.H.C. Crick described, right-handed DNA double helix (B-DNA;see fig. Tab.), Which is characterized by its high elasticity, there are other double helix shapes. The one that also rotates to the right A-DNA, in which the sugar is in a different conformation, which affects the orientation of the phosphodiester bonds and the glycosidic bonds, occurs depending on the sequence with a low water content and with lithium as the counterion (in addition, DNA / RNA hybrids and all double -stranded sections of RNAs occur in the A-shape in front; see fig., See table). Another conformation with a right-handed helix is ​​the so-called. C-DNA. Based on the natural B-shape, loc P-DNA (for "Pauling-like" DNA, since LC Pauling postulated a similar shape for DNA before the discovery of the B-DNA double helix) designated overextended conformation can be obtained in which only 2.6 base pairs occur per helix turn and which are 75% longer than the B shape is. The sugar-phosphate backbone of the P-DNA is on the inside, the bases point outwards unpaired. A left-turning form, the so-called. Z-DNA (cf. Fig., cf. Tab.), in which the two sugar-phosphate backbones form a zigzag shape (but overall helical), can exist in strands with alternating purine and pyrimidine bases. The Z-shape can also occur within a B-DNA helix and is z. B. stabilized by negative torsional stress, high ionic strengths or 5-substitution on cytosine residues. It is controversial whether all of these forms can also develop under physiological conditions. In the course of transcription, negative torsional tension is created behind the RNA polymerase, which among other things Z-DNA could stabilize; the positive torsional tension built up in the front of the RNA polymerase could stabilize P-DNA. Various forms would allow the selective binding of proteins and other ligands. In the meantime, four-stranded structures of DNA have also been discovered, which can form on sequences rich in guanine or cytosine (see info box). Further spirals superimposed on the turns of the DNA double helix are created supercoilForms (supercoil). These are caused both by the cation environment surrounding the DNA and by the binding of DNA to certain proteins, in the case of nucleated cells especially to the histones (chromatin), and thus lead to the more densely compressed structures of the Chromatids other Chromosomes, which can already be seen in the light microscope after staining.
Occurrence: The majority of DNA is located in the chromosomes of the nucleated cells of the eukaryotes (eucyte) or in the chromosome-like structures (bacterial chromosome, nucleoid) of the prokaryotes (protocyte). On top of that comes DNA extrachromosomal (extrachromosomal hereditary factors) in the mitochondria (chondroma) and plastids (plastom) and as such forms the basis for the semi-autonomous character of these organelles or for extrachromosomal, i.e. H. Inheritance of certain characteristics that do not obey Mendel's rules. Bacteria and other microorganisms also often have extrachromosomal DNA, so-called. Plasmids or Episomes, which are characterized by their transferability between individual tribes. This transferability together with their small size (mostly only a few thousand base pairs) and the increased occurrence of resistance genes on plasmids (resistance factors) has led to their use as cloning vectors (cloning) in the context of genetic engineering.
Modifications: The DNAs of some viruses and bacteriophages contain the base 5-hydroxymethyluracil instead of thymine or the base 5-hydroxymethylcytosine instead of cytosine. To a very small extent (0.1% and less), bacterial DNA chains also contain monomer units with the bases 5-methylcytosine and N-6-methyladenine (base methylation, DNA methylation) modified by methylation. Since the methyl groups of these bases in the cell only after the chains have been built, i.e. H. post-replicative, they act as indicators to distinguish between parental (= already methylated) DNA strands and DNA daughter strands (not yet methylated for a limited time after replication) and thus allow DNA repair processes (DNA repair) to preferential repair of DNA daughter strands (to the mutation triggered by 5-methylcytosine: deamination). In the DNA of eukaryotic organisms, cytosine is converted to 5-methylcytosine to a much greater extent (in animals up to 2%, in algae up to 3.5%, in plants up to 10%, based on the total base composition). In the meantime it has been established that the C-methylation of eukaryotic DNA has an influence on the state of regulation (gene regulation) of the genes concerned. Ribonucleotides can also be found in small amounts in DNA chains in the form of short RNA primers made up of only 3–20 ribonucleoside monophosphates, which are required to start DNA replication. They are either built in temporarily or survive as "replication relics". They are to be distinguished from the RNA chains which are not covalently bound to DNA via RNA polymerase and which form as a template during the transcription of genetic information on DNA.
Chain length: The size of DNA chains (see table) ranges between several thousand (plasmids, phage DNAs, mitochondrial DNA, plastid DNA) and many millions (bacteria, plants, fungi, animals, humans) base pairs, although the total DNA of nucleated organisms is not present in a single chain, but distributed over several chromosomes - correspondingly several chains. (In addition, the extra chromosomal DNAs of the mitochondria and plastids, which are present in the relevant organelles in a larger number of copies, are added as separate chains.) Each chromatid fiber of a chromosome contains a continuous DNA double strand, the length of which, depending on the size of the chromosome concerned, between 2 and 2 million and 200 million base pairs, corresponding to a relative molecular mass of 1.2 billion to 120 billion. The chain length of DNA molecules therefore exceeds that of the other linear macromolecules (polysaccharides, proteins, RNA) occurring in the cell by several orders of magnitude. Given these extraordinary chain lengths, the capacity of DNA to store information appears to be practically unlimited. In addition there is the simple combinatorial relationship, which means that for a chain composed of 4 different elements with n Chain left 4n possible sequences, d. H. 16 (= 42) different dinucleotide sequences, 64 (= 43) different trinucleotide sequences, 256 (= 44) various tetranucleotide sequences, etc. exist. Even for the chain length of an average one Gens 1000 base pairs result in the unimaginably high number of 41000 Sequence possibilities and correspondingly huge orders of magnitude for the genomes of the organisms made up of several million base pairs. From this it follows that during the biological evolution, which lasted about 3.5 billion years, only a tiny fraction of the theoretically possible nucleotide sequences could be realized in the form of DNA, and of this only a small fraction exists in the totality of the organisms living today.
Repetitive sequences: Typical of DNA in nucleated organisms is the occurrence of repetitive sequences (sequence repetitions; repetitive DNA), the proportion of which in total DNA varies between 10% and a maximum of 80% depending on the species. Repetitive sequences (see Infobox) are particularly common in plants and contribute to the sometimes enormous differences in genome sizes that exist within plant families, but often also between different tissues of the same species. The sequence analysis of individual repetitive sequences has shown that the repeating units differ from one another in individual positions, so that repetitive DNA sequences are not to be understood as strict repetitions, but rather as variations on certain "basic themes". Because of their "monotonous" character, repetitive DNA sequences do not contain any genes (exception see below), and despite numerous speculations, the question of possible other functions of repetitive DNA must not yet be resolved. This has inter alia. to the hypothesis of the so-called "selfish" DNA (engl. selfish DNA;selfish genes), according to which the existence of certain DNA sequences does not contribute to promoting the chances of survival of the species in question (but also does not reduce them or does not reduce them enough to cause extinction of the species in question), so that repetitive DNA - just like the intervening sequences (gene mosaic structure) of split genes - without a meaningful function for the species in question, as a stowaway, as it were, contained in their DNA and thus only to be regarded as caring for their own ("selfish") replication. A possible meaning has only been found for microsatellites (satellite DNA). Many of these sequences lie within genes. It is very likely that they can be shortened or lengthened in the course of DNA replication, which leads to the shifting of subsequent base triplets with corresponding effects on protein synthesis. In this way, they could contribute to an acceleration of evolution, but with the disadvantage of often disadvantageous mutation events. The group of so-called "unique" sequences usually contains the genes of an organism. An exception are the genes for ribosomal RNA (ribosomes), which are located in 50–1000 copies in the so-called nucleolus organizer (chromosomes, nucleolus) or after amplification (gene amplification) in many thousands of copies in nucleolus DNA and are therefore localized are contained in the fraction of the medium repetitive DNA sequences. Another exception are the genes coding for histones, which are represented in 250–500 copies. DNAs of seedless organisms, e.g. B. the bacterium Escherichia coli, do not contain any repetitive sequences, with the exception of extrachromosomal plasmid DNAs, whose copy numbers can go up to 100, and genes for ribosomal RNA that z. B. at Escherichia coli in 7 times, at Bacillus subtilis (Bacillus) occur in 10 copies are to be mentioned.
- The synthesis of DNA takes place in the cell through semi-conservative replication under the catalytic action of several enzymes, especially DNA polymerases, DNA ligases and DNA gyrases (DNA topoisomerases). The 4 2´-deoxyribonucleoside-5´-triphosphates are converted as activated monomer building blocks with cleavage of pyrophosphate. In addition to DNA replication, DNA syntheses also take place as partial steps in certain processes of DNA repair and DNA recombination. However, these DNA syntheses are limited to smaller areas of the DNA chains. With the help of a combination of organic-chemical and enzymatic methods, DNA syntheses or gene syntheses are also possible in the test tube and have recently been used increasingly in genetic engineering projects (genetic engineering).
- The Dismantling of DNA occurs through hydrolysis under the catalytic action of deoxyribonucleases. In the test tube, DNA can be degraded by the action of acids, which preferably leads to the cleavage of the purine bases (adenine and guanine) with the formation of apuric acid, and subsequent alkali hydrolysis at the purine-free positions to form a mixture of different deoxy-oligonucleotides. Dimethyl sulfate and other alkylating substances lead preferentially to the alkylation of the purines, most strongly in the 7-position of guanine. As a result, the N-glycosidic bonds of the purine bases are loosened, so that the latter detach from the sugar-phosphate backbone and thereby lead to apurine positions (when the reaction is complete, to apuric acid). In contrast, hydrazine and hydroxylamine attack the pyrimidine bases selectively and lead to cleavage and detachment of the pyrimidine structure (pyrimidine) with the formation of apyrimidine positions (when the reaction is complete, to apyrimidic acid). The sugar-phosphate backbone can be broken at both the apurine and the apyrimidine positions by subsequent alkali treatment, which is equivalent to DNA single-strand breaks ultimately induced by the reagents mentioned. These reaction sequences, which show increased base specificity under special conditions, form the basis of the method for DNA sequence analysis (sequencing) developed by A. Maxam and W. Gilbert. On the other hand, reactions of DNA in the cell with these and numerous other, but mechanistically similar acting chemical agents lead to the triggering of mutations.
- Significant contributions to the research of deoxyribonucleic acids (see info box) were made, inter alia. O.T. Avery, E. Chargaff, F.H.C. Crick, R.J.W. Feulgen, R.E. Franklin, A.D. Hershey, P. Levene, F. Sanger, J.D. Watson, M.H.F. Wilkins. DNA computers, DNA fingerprinting, DNA sequencers, DNA synthesizers. Transcription translation;

Deoxyribonucleic Acids I.
Deoxyribonucleic Acids II
Deoxyribonucleic Acids III.

H.K./M.B.

Lit .:Sinden, R.R .: DNA structure and function. San Diego 1994. Watson, J.D .: The double helix. Hamburg 1997.

Deoxyribonucleic acids
Section from a single strand of DNA with the tetra-nucleotide sequence ACGT (in the conventional 5 ' 3 'direction, d. H. from the 5 'end to the 3' end, read). Note that the horizontal P-O-CH2-Bondings are shown significantly overstretched for reasons of spatial representation and are in reality the same length as the vertical P-O bonds. Compare this with the spherical model reproduced in the illustration of deoxyribonucleic acids I, which correctly reproduces the atomic distances of the deoxyribose-phosphate backbone (in which, however, the bonds between deoxyribose and the bases are overstretched). Note also that another of the 256 theoretically possible tetranucleotide sequences, namely TGCA, is shown in the panel.

 

Deoxyribonucleic acids
Z = Pentose sugar 2-deoxyribose, P. = Phosphoric acid, A. = Adenine, G = Guanine, C. = Cytosines, T = Thymines
Double strand model (Double helix) a DNA.
On the left a schematic section of 19 base pairs (= almost 2 turns), on the right as a molecular model slightly enlarged and therefore as a slightly smaller section of only 16 base pairs. Note the two differently sized furrows running parallel to the two sugar-phosphate backbones, which are called large and small furrows, respectively; through this the bases are accessible to a considerable extent from the outside despite their packaging inside the double helix and despite the mutual pairing. This is of great importance for the interaction of proteins with a regulatory effect (including repressors, activators, RNA polymerase), since it allows "scanning" or "recognizing" specific nucleotide sequences without breaking the double helix. The thickness of the double helix, corresponding to the greatest width of the right model, is 1.9 nm (= 1.9 x 10–6 mm); the length of a helical turn, which corresponds almost exactly to 10 base pairs, is 3.4 nm. The length of an uncoiled DNA of 106 Base pairs are calculated to be 3.4 105 nm = 0.34 mm; accordingly it is approx. 4 · 106 Base pair DNA of the bacterium E. coli when stretched, about 1.3 mm long. The total DNA of a single human egg cell or sperm cell with about 3 x 109 Base pairs add up to a length of about 1 m.

Deoxyribonucleic acids
Recent research results: Recent studies (1999) indicate that DNA - at least in a vacuum or over short distances - electrically conductive is. However, how the charges are transported and how the sequence of bases in the molecule influences the transport is controversial; the results vary depending on experimental parameters.Possible applications of these findings would be the detection of mutations by measuring conductivity or the production of one-dimensional cables from DNA for miniature machines.
The uptake of DNA from the food is easier than previously assumed (before 1998). Studies on mice show that deoxyribonucleic acids from food or from intestinal bacteria partially survive the intestinal passage intact and are absorbed. They reach the liver and spleen via blood cells, where they can apparently be integrated into the genome of various cells. The deoxyribonucleic acids can also get into the genome of cells of the offspring via germline cells. If they are expressed there, this can lead to the formation of antibodies against the corresponding proteins / protein fragments. However, this is unlikely to result in any safety-related problems for the use of genetic engineering in food production, because humans have obviously always been exposed to the influence of foreign genes without this having had any serious effects (e.g. possibly carcinogenic).
Enzymatically active ribonucleic acids (ribozymes) have been known for a long time. Investigations with variants of certain deoxyribonucleic acids, which were produced by means of in vitro evolution, have now also been found to be diverse catalytic Properties of deoxyribonucleic acids.
In addition to the well-known double helix structures, four-strand Structures of DNA described. Guanine-rich sections, as are often found in the eukaryotic genome in regulatory sequences or the telomeres Quadruplex DNAs, which are stabilized by quartet of cyclically bound guanine residues and at the ends of which there are loops of thymine residues. Cytosine-rich sections also form quadruplex DNA, but with a different structure. Two parallel double strands intercalate with each other and are stabilized by hemiprotonated cytosine-cytosine base pairs.


Deoxyribonucleic acids
Sizes of DNA or size of the haploid genome of selected organisms (sorted by DNA content)
DNA or organism DNA content (pg) length+ Base pairs+
Plasmid pBR322
from Escherichia coli
0,0000045 1.4 µm 4363
SV40 0,0000055 1.78 µm 5243
Bacteriophage ΦX174 0,0000059 1.83 µm 5386
Bacteriophage M13 0,0000072 2.18 µm 6407
Bacteriophage T7 0,000044 13.6 µm 39 936
Bacteriophage λ 0,000055 16.5 µm 48 502
Bacteriophage T4 0,0002 56 μm 1,66 · 105
Haemophilus influenzae 0,0020 622 μm 1,830 · 106
Escherichia coli 0,0052 1.6 mm 4,72 · 106
Yeast (Saccharomyces
cerevisiae)
0,0132 4.1 mm 1,2025 · 107
Roundworm (Caenorhab-
ditis elegans)
0,0835 24 mm 9,7 · 107
Drosophila (Drosophila
melanogaster)
0,18 56 mm 1,65 · 108
Mouse (mus musculus) 2,5 0.75 m 3,0 · 109
Clawed Frog (Xenopus
laevis)
3,1 0.95 m 3,1 · 109
Human (homo sapiens) 3,2 0.99 m 3,3 · 109
Corn (Zea mays) 7,3 2.2 m 6,6 · 109
Onion (Allium
cepa)
16,5 5.1 m 1,5 · 1010
Mitochondrial DNA:
homo sapiens 0,0000182 5.6 µm 16 569
Saccharomyces cerevisiae 0,000081 25 μm 75 000
Arabidopsis thaliana
0,00041 126 μm 3,72 · 105
Chloroplasts:
Zea mays 0,000155 47 μm 1,40 · 105

1 picogram [pg] = 10–12G. One picogram of DNA contains approx. 9.1 x 108 = approx. 910 million base pairs and is approx. 309 mm long when decondensed.
+ The DNA lengths, usually determined by electron microscopy, and the number of base pairs often only approximate the relationship 340 nm
1000 base pairs. In the case of the shorter DNA chains, the deviations are due to the uncertainty of the length measurements, in the case of the more complex DNAs they are also due to the increasingly imprecise determination of the base pair numbers with the chain lengths.

Deoxyribonucleic acids
electron micrograph of a DNA molecule