According to AbbreviationFinder, DNA is a double-stranded molecule, that is, it is made up of two chains arranged in an antiparallel way and with the nitrogenous bases facing each other. In its three-dimensional structure, different levels are distinguished: Hib, J. & De Robertis, EDP 1998. Fundamentals of Cellular and Molecular Biology. El Ateneo, 3rd edition, 416 pages. ISBN 950-02-0372-3. ISBN 978-950-02-0372-2De Robertis, EDP 1998. Cellular and Molecular Biology. The Athenaeum, 617 pages. ISBN 950-02-0364-2. ISBN 978-950-02-0364-7
- Primary structure:
- Chained nucleotide sequence. It is in these chains where the genetic information is found, and since the skeleton is the same for all, the difference in information lies in the different sequence of nitrogenous bases. This sequence presents a code, which determines one information or another, according to the order of the bases.
- Secondary structure:
- It is a double helix structure. It allows to explain the storage of genetic information and the mechanism of DNA duplication. It was postulated by Watson and Crick, based on X-ray diffraction carried out by Franklin and Wilkins, and on the Chargaff base equivalence, according to which the sum of adenines plus guanines equals the sum of thymines plus cytosines.
- It is a double stranded, right-handed or left-handed, depending on the type of DNA. Both chains are complementary, since adenine and guanine from one chain bind, respectively, to thymine and cytosine from the other. Both chains are antiparallel, since the 3 ‘end of one faces the 5’ end of the homologous.
- There are three models of DNA. Type B DNA is the most abundant and is the one discovered by Watson and Crick.
- Tertiary structure:
- It refers to how DNA is stored in a small space, to form Chromosomes. It varies depending on whether it is Prokaryotic or Eukaryoticorganisms:
- In Prokaryotes, DNA folds like a super-helix, generally in a circular shape and associated with a small amount of proteins. The same occurs in cellular organelles such as mitochondria and in chloroplasts.
- In Eukaryotes, given that the amount of DNA in each Chromosome is very large, the packaging has to be more complex and compact; for this, the presence of proteins is needed, such as Histones and other proteins of a non-histonic nature (in Spermatozoa these proteins are Protamines).
Double helix structures
DNA exists in many conformations. However, only the DNA-A, DNA-B, and DNA-Z conformations have been observed in living organisms. The conformation that DNA adopts depends on its sequence, the amount and direction of supercoiling it presents, the presence of chemical modifications in the bases and the conditions of the solution, such as the concentration of Metal Ions and Polyamines. Of the three conformations., the “B” form is the most common in the conditions existing in cells. The two alternative double helices of DNA differ in their geometry and dimensions.
Shape “A” is a right-turning spiral, wider than “B”, with a shallow and wider minor cleft, and a narrower and deeper major cleft. The “A” form occurs under non-physiological conditions in dehydrated forms of DNA, while in the cell it can occur in hybrid DNA-RNA strand pairings, as well as enzyme-DNA complexes.
DNA segments in which the bases have been modified by methylation can undergo major conformational changes and adopt the “Z” shape. In this case, the strands rotate around the axis of the helix in a left-hand spiral, the opposite of the more common “B” shape. These rare structures can be recognized by specific proteins that bind to Z-DNA and are possibly involved in the regulation of transcription.
Quadruplex structures
At the ends of linear chromosomes are specialized regions of DNA called Telomeres. The main function of these regions is to allow the cell to replicate the chromosome ends using the Telomerase enzyme, since the enzymes that replicate the rest of the DNA cannot copy the 3 ‘ends of the chromosomes. These specialized chromosomal endings also protect the ends of the DNA, and prevent the DNA Repair systems in the cell from processing them as damaged DNA that must be corrected.
In human cells, telomeres are long areas of single-stranded DNA that contain a few thousand repeats of a single TTAGGG sequence. These guanine-rich sequences can stabilize chromosomal ends by forming stacked set structures of four-base units, rather than the base pairs normally found in other DNA structures. In this case, four guanine bases form flat-topped units that stack on top of each other to form a stable quadruplex-G structure. These structures are stabilized by forming hydrogen bonds between the ends of the bases and chelation of an ionic metal in the center of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or from several different parallel strands, each contributing a base to the central structure.
In addition to these stacked structures, Telomeres also form long looped structures, called telomeric loops or T-loops (T-loops). In this case, the single strands of DNA twist on themselves in a wide circle stabilized by proteins that bind to telomeres.At the end of the T-loop, the single-stranded telomeric DNA is attached to a region of double-stranded DNA. strand because the telomeric DNA strand alters the double helix and pairs to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.
Major and minor clefts
The Double Helix is a Right-handed spiral, that is, each one of the Nucleotide chains turns to the right; This can be verified if we look, going from bottom to top, in the direction followed by the segments of the strands that are in the foreground. If the two strands turn to the right the double helix is said to be right-handed, and if they turn to the left, left- handed (this shape can appear in alternative helices due to conformational changes in the DNA). But in the most common conformation that DNA adopts, the double helix is right-handed, each base pair turning about 36º with respect to the previous one.
When the two strands of DNA are wound one over the other (either to the right or to the left), gaps or slits are formed between one strand and the other, exposing the sides of the Nitrogen Bases inside (see the animation). In the most common conformation that DNA adopts, there appear, as a consequence of the angles formed between the sugars of both chains of each pair of nitrogenous bases, two types of clefts around the surface of the double helix: one of them, the cleft o major groove, which is 22 Å (2.2 Nm) wide, and the other, the lesser groove or groove, which is 12 Å (1.2 nm) wide.
Each turn of the helix, which is when it has made a 360º turn or what is the same, from the beginning of the major cleft to the end of the minor cleft, will therefore measure 34 Å, and in each of these turns there are about 10, 5 bp. left || 300px | thumb | Major and minor indentations of the double helix. The greater width of the cleft implies that the ends of the bases are more accessible in it, so that the amount of exposed chemical groups is also greater, which facilitates the differentiation between the base pairs AT, TA, CG, GC.
As a consequence, the recognition of DNA sequences by different proteins will also be facilitated without the need to open the double helix. Thus, proteins such as transcription factors that can bind to specific sequences, frequently contact the sides of the bases exposed in the major cleft. On the contrary, the chemical groups that are exposed in the minor cleft are similar, so that the base pair recognition is more difficult; hence the greater cleft is said to contain more information than the lesser cleft.
Sense and antisense
A DNA sequence is called ” sense ” (in English, sense) if its sequence is the same as the sequence of a messenger RNA that is translated into protein. The sequence of the complementary DNA strand is called “antisense” (antisense). In both strands of DNA of the double helix, there can be both sense sequences, which encode mRNA, and antisense, which do not encode it, that is, the sequences that encode mRNA are not all present in a single strand, but rather distributed among the strands. two strands. In both Prokaryotes and Eukaryotes, RNAs with sequences antisense, but the function of these RNAs is not completely clear.
It has been proposed that antisense RNAs are involved in the regulation of gene expression through RNA-RNA pairing: Antisense RNAs would pair with complementary mRNAs, thus blocking their translation.
In a few DNA sequences in prokaryotes and eukaryotes (this fact is more frequent in plasmids and viruses), the distinction between sense and antisense strands is more diffuse, because they have overlapping genes. dual function, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded in their tiny genomes.
Supercoiling
DNA can be twisted like a string in a process called DNA supercoiling. When DNA is in a “relaxed” state, a strand normally rotates around the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands may be tied more tightly or more loosely.
If the DNA is twisted in the direction of the helix, the supercoil is said to be positive, and the bases are held together more closely. If the DNA is twisted in the opposite direction, the supercoil is called negative, and the bases move away. In nature, most DNA has a slight negative supercoiling that is produced by enzymes called topoisomerases. These enzymes are also necessary to release the torsional forces introduced into DNA strands during processes such as Transcription and Replication.
Base modifications
The expression of genes is influenced by the way DNA is packed into chromosomes, in a structure called Chromatin. The base modifications may be involved in packaging of DNA: the regions that have low gene expression or null typically contain high levels of methylation of the bases cytosine. For example, cytosine methylation produces 5-methyl-cytosine, which is important for the inactivation of the X Chromosome. The mean level of methylation varies between organisms: the Caenorhabditis elegans worm lacks cytosine methylation, while Vertebrates have a high level – up to 1% of their DNA contains 5-methyl-cytosine. Despite the importance of 5-methyl-cytosine, it can be deaminated to generate a thymine base. Methylated cytosines are therefore particularly sensitive to mutations. Other base modifications include the methylation of Adenine in Bacteria and the Glycosylation of Uracil to produce the “J-base” in Kinetoplasts.
DNA damage
DNA can be damaged by many types of Mutagens, which change the sequence of DNA: alkylating agents, as well as high-energy electromagnetic radiation, such as UV light and X-rays.
The type of DNA damage occurs depends on the type of mutagen. For example, UV light can damage DNA producing Thymine dimers, which are formed by cross-linking between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple damages, including modifications of bases, especially guanine, and double-strand breaks.
In any given human cell, about 500 bases suffer oxidative damage every day.Of these oxidative injuries, the most dangerous are double-stranded breaks, since they are difficult to repair and can produce point mutations, insertions and deletions of the sequence of DNA, as well as chromosomal translocations.
Many mutagens are positioned between two adjacent base pairs, which is why they are called intercalating agents. Most intercalating agents are flat, aromatic molecules, such as Ethidium Bromide, Daunomycin, Doxorubicin, and Thalidomide.
In order for an intercalating agent to be integrated between two base pairs, they must separate, distorting the DNA strands and opening the double helix. This inhibits DNA Transcription and Replication, causing toxicity and mutations. Therefore, DNA intercalating agents are often Carcinogens: Benzopyrene, Acridines, Aflatoxin, and Ethidium Bromide are well-known examples. However, due to their ability to inhibit DNA replication and transcription, these toxins they are also used in chemotherapy to inhibit the rapid growth of cancer cells.
DNA damage initiates a response that activates different repair mechanisms that recognize specific DNA lesions, which are repaired on the spot to recover the original DNA sequence. Likewise, DNA damage causes a stop in the cell cycle, which leads to the alteration of numerous physiological processes, which in turn involves protein synthesis, transport and degradation (see also DNA damage checkpoint). Alternatively, if the genomic damage is too great to be repaired, the control mechanisms will induce the activation of a series of cellular pathways that will culminate in cell death.
