What happens to the complementary base when the other undergoes a base substitution mutation?

What happens to the complementary base when the other undergoes a base substitution mutation?

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From what I know only the base pairs A and T/U, or G and C can occur due to hydrogen bonding. So if a base substitution mutation occurs, say an A is replaced by a C on the strand, does it affect only one of the strands on the DNA or does it changes the base pair entirely? Thanks.

Consider a stretch of DNA


Let's say that during replication a nucleotide get switched


Now, this does not work. The cellular machinery will find this location and try to solve it. It will either resolve it as


and no mutation would have happened. Or it will solve it as


and a mutation just happened.

You might want to read about DNA repair mechanisms.

A base substitution mutation often occur during replication of DNA. Remember that the template strand is methylated, in order to understand who will be the new synthetized strand between both.

Having this scenario, with a nucleotide substitution mutation in the 3rd position from 5' , the 5'-3' strand is the fresh synthetized.

The DNA polymerase will trait just the 5'-3' strand as something to work on : if a mutation happens the proof-reading activity of the DNA polymerase will try to cut off the wrong base, and to re-synthetize this piece of the strand.

5'- A G G T T C G -3' --> new strand 3'- T C A A A G C -5' --> template

If it isn't able to figure the mutation, it'll be fixed in the next replication process, so the mutation will be fixed into the considered DNA.

What happens to the complementary base when the other undergoes a base substitution mutation? - Biology

There are many different ways that DNA can be changed, resulting in different types of mutation. Here is a quick summary of a few of these:

  1. change a codon to one that encodes a different amino acid and cause a small change in the protein produced. For example, sickle cell anemia is caused by a substitution in the beta-hemoglobin gene, which alters a single amino acid in the protein produced.
  2. change a codon to one that encodes the same amino acid and causes no change in the protein produced. These are called silent mutations.
  3. change an amino-acid-coding codon to a single "stop" codon and cause an incomplete protein. This can have serious effects since the incomplete protein probably won't function.

For example, consider the sentence, "The fat cat sat." Each word represents a codon. If we delete the first letter and parse the sentence in the same way, it doesn't make sense.

In frameshifts, a similar error occurs at the DNA level, causing the codons to be parsed incorrectly. This usually generates truncated proteins that are as useless as "hef atc ats at" is uninformative.

There are other types of mutations as well, but this short list should give you an idea of the possibilities.

Aqa a level biology 2020 UNOFFICIAL MARKSCHEME

Hi has anyone sat the 2020 paper 1? could you please help us by trying to make an unofficial mark scheme?
this is what I remember :

1.1. function of app hydrolase? catalyses the hydrolysis of ATP into ADP+Pi (M1) to release energy needed for transport of substance by carrier proteins, process is active transport which requires energy (M2) ,you can write the equation

1.2. explain movement of Na+? not sure about M1, low conc of Na+ in cell so Na+ moves from lumen to cell carrying glucose with it, co-transport (M2)

1.3. 2 features in cells specialised for absorption? (2)
1.4. drawing of phospholipid (2)
1.5. how amino acids join to form a polypeptide so there is always NH2 at one end and COOH at the other(2)
M1 peptide bond M2:
2.1. explain differences in table 1: (3)
2.2. explain why (2)
2.3. describe the role of micelles in the absorption of fats into the cells lining the ilium (3)
Micelles increase the surface area for lipase to act on, which means faster hydrolysis action by lipase. Micelles are water soluble vesicle and so deliver fatty acids and glycerol to the epthelial cells of the ileum for absorption .
3.1. explain why (3)
3.2. there is a small increase in pressure and in rate of blood flow in the aorta. explain how this happens and its importance(2)
3.3. describe one way in which the student's curve would be similar to and one way it would be different from the curve shown. (2)
3.4 calculate heart rate (1)
4.1. tick box 2
4.2. two variables to keep constant: water temperature, concentration of acid
4.3 membrane structure (4)
4.4. describe a method to prepare colour standards and use them to give data for the total. (3)
5.1. describe role of DNA polymerase (2) joins free floating nucleotides by comp base pairing, forms phosphodiester bond, its a bond reaction
5.2. calculate time diff as a percentage (2)
5.3. describe how an enzyme can be phosphorylated (2)
5.4. why higher conc could cause a tumor? (2)
cells go through DNA rep earlier, more DNA rep, rep is uncontrollable, results in a mass of cells

6.1. why death of alveolar epithellium cells reduces gas exchange in human lungs(3)

10.1 describe how mRNA is formed by transcription in eukaryotes(5)
DNA helicase unwinds DNA strands breaking hydrogen bonds between them(M1). One of the strands acts as a template strand. Free RNA bases attach to complementary bases on template strand forming complementary base pairing. DNA polymerase joins the nucleotides together forming phosphodiester bonds between them(M6). This forms pre mRNA. Pre mRNA undergoes splicing(M7), removing non-coding DNA which is introns and exons remain. Mature mRNA is formed.

10.2. describe how a polypeptide is formed by translation of mRNA (6)

10.3. define gene mutation and explain how it can have no effect on an individual and a positive on. (4)
Gene mutation is a change in DNA base sequence(M1). Dna is degenerate and so more than one codon can code for the same amino acid, so base substitution will have not effect(M2). However, base addition and deletion can cause an effect as it changes the amino acid being coded for and therefore can produce non functional proteins

What would be the effect of a substitution in one of the nucleotides?

Then, what effect does a substitution mutation have on a protein?

A mutation in DNA alters the mRNA, which in turn can alter the amino acid chain. A base substitution may have three different effects on an organism's protein. It can cause a missense mutation, which switches one amino acid in the chain for another.

Likewise, what can be the result of changes in gene codes? As such, the nucleotide sequences found within it are subject to change as the result of a phenomenon called mutation. Depending on how a particular mutation modifies an organism's genetic makeup, it can prove harmless, helpful, or even hurtful.

In this way, what would be the effect of a deletion or an addition in one of the DNA nucleotides?

Called a frameshift mutation, an insertion or deletion can affect every codon in a particular genetic sequence by throwing the entire three by three codon structure out of whack. In other words, every single codon would code for a new amino acid, resulting in completely different proteins coded for during translation.

What are the 3 types of substitution mutations?

Substitution mutations can be good, bad, or have no effect. They cause three specific types of point mutation: silent, missense, and nonsense mutations. A silent mutation is a mutation where the function of the protein is not changed. A missense mutation codes for the wrong protein.

General DNA Repair

The two methods above are specifically related to errors and fixes surrounding the replication process. While many genetic coding errors occur during the replication process, that isn&rsquot the only source of mutations or damage in our DNA! Our genetic material can also be damaged as a result of radiation, chemicals and other external sources. Thus, there also need to be repair processes for DNA when the damage occurs during the normal life of a cell.

The simplest version of this repair is simply damage reversal, which is typically required in response to chemical exposure. When certain chemicals enter the cell, those molecules or groups may bind to the nucleotide bases of the DNA, thus altering how they pair during replication. This mis-pairing could lead to mutations, but our cells have mechanisms to remove such additional, unwanted molecules and ensure that the bases behave normally during replication.

Base excision repair is a quick and simple replacement process, in which a single mis-paired base (one that changed through chemical interaction, or by slipping through both proofreading and mismatch repair processes) must be removed and replaced. An enzyme will detect this incorrect nucleotide base, bind to the strand, and remove the incorrect base. A polymerase will come to fill in the gap with the right base, and an enzyme called ligase will seal up the DNA backbone.

Nucleotide excision repair is a bit more complicated, as these &ldquoerrors&rdquo in the DNA strand often involve more than one base pair, or a short chunk of the genetic code. As mentioned above, when certain chemical groups bind to our DNA, they can change the behavior and replication accuracy of the strand. Damage from radiation can cause sections of DNA to interact with itself, thus leading to mutations. These damaged sections of DNA will be addressed by DNA helicase, which cracks open the strand and wrinkles the strand around the damaged section of DNA. That entire section will be removed, a DNA polymerase will organize and place the correct and undamaged base pairs, and ligase will once again seal the gap where the repair work was done.

Finally, if the entire DNA strand breaks, or both sides of the strand have become damaged and require replacement, double-stranded break repair comes into play. There are two varieties of this repair, one that simply sticks the broken halves back together, with the addition of some extra nucleotides. These act like &ldquoglue&rdquo, and will likely cause some mutations, but it is a better solution than allowing hundreds of genes and large sections of chromosomes to be forever separated and lost. The more delicate double-stranded method involves recombination from the non-damaged homologue of the chromosome. The two homologues come together in the cell and the damaged section is directly copied and reconstituted from the undamaged partner. This form of repair does not usually result in additional mutations.

Point mutation

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Point mutation, change within a gene in which one base pair in the DNA sequence is altered. Point mutations are frequently the result of mistakes made during DNA replication, although modification of DNA, such as through exposure to X-rays or to ultraviolet radiation, also can induce point mutations.

There are two types of point mutations: transition mutations and transversion mutations. Transition mutations occur when a pyrimidine base (i.e., thymine [T] or cytosine [C]) substitutes for another pyrimidine base or when a purine base (i.e., adenine [A] or guanine [G]) substitutes for another purine base. In double-stranded DNA each of the bases pairs with a specific partner on the corresponding strand—A pairs with T and C pairs with G. Thus, an example of a transition mutation is a GC base pair that replaces a wild type (or naturally occurring) AT base pair. In contrast, transversion mutations occur when a purine base substitutes for a pyrimidine base, or vice versa for example, when a TA or CG pair replaces the wild type AT pair.

At the level of translation, when RNA copied from DNA is converted into a string of amino acids during protein synthesis, point mutations often manifest as functional changes in the final protein product. Thus, there exist functional groupings for point mutations. These groupings are divided into silent mutations, missense mutations, and nonsense mutations. Silent mutations result in a new codon (a triplet nucleotide sequence in RNA) that codes for the same amino acid as the wild type codon in that position. In some silent mutations the codon codes for a different amino acid that happens to have the same properties as the amino acid produced by the wild type codon. Missense mutations involve substitutions that result in functionally different amino acids these can lead to alteration or loss of protein function. Nonsense mutations, which are a severe type of base substitution, result in a stop codon in a position where there was not one before, which causes the premature termination of protein synthesis and, more than likely, a complete loss of function in the finished protein.

Some scientists recognize another type of mutation, called a frameshift mutation, as a type of point mutation. Frameshift mutations can lead to drastic loss of function and occur through the addition or deletion of one or more DNA bases. In a protein-coding gene the sequence of codons starting with AUG (where U is the RNA base uracil, which replaces T during transcription) and ending with a termination codon is called the reading frame. If a nucleotide pair is added to or subtracted from this sequence, the reading frame from that point will be shifted by one nucleotide pair, and all of the codons downstream will be altered. The result will be a protein whose first section (before the mutational site) is that of the wild type amino acid sequence, followed by a tail of functionally meaningless amino acids.

How Mutations May be Induced? | Biology

Mutations may be induced by many agents called mutagens. These may be chemical mutagens and radiations, e.g., X-rays, y-rays and UV rays.

Image Courtesy :

Mutations are created at molecular level by altering the base in nuleotides. Alternations are created by:

(a) Deletion of base (b) Inversion of base (c) Inversion of bases and (d) replacement of base pairs.

Replacement of base pair takes place during replication of DNA without breaking DNA. It may be of two types. (Fig. 40.15)

Purine is replaced by another purine or pyrimidine is replaced by another pyrimidine.

Purine is replaced by pyrimidine.

The discovery of mutagenic effects produced by various types of radiations was shown for the first time as an experimental probe for changine gene structure and function. It was very difficult to distinguish between direct or indirect effects of irradiation and to analyse the exact nature of biochemical compounds produced. Chemical mutagens are more effective and their results are characterized.

Thomas and Steinberg found nitrous acid effective causing mutation in Aspergillus. Auerbach and Robson found that mutations can be induced by nitrogen and sulphur gas in Drosophila. Mutagenic activity in formaldehyde, diethylsulfate, diazomethane, etc., are discovered by Rapoport. Chemical mutagens cause severe skin irritations in mammals and also can produce cancer.

There are some chemicals which affect some organisms but not other. Watson and Crick were first to suggest that mutation could occur as a result of occasional changes in the hydrogen bonding of nucletodie bases, e.g., adenine normally bears an NH2 (amino) group providing hydrogen atom for bonding with the complementary keto (C = O) group of thymine. In a Tautomeric shift the amino group is changed to amino group (NH). This base now bonds with cytosine (instead of thymine). In thymine the tautomeric shift from keto to enol (COH) form allows it to bond with guanine (instead of adenine) (Fig. 40.16).

If the tautomeric shift produces the error, it is necessary that DNA replication should take place.

A chemical substance resembling a base is called base analogue. It may be incorporated into newly synthesized DNA instead of a normal base. Pyrimidine analogue 5-bromouracil (5-BU) is structurally similar to thymine. 5-chlorouracil (5 CU) and 5 iodouracil (5 IU) can also replace thymine in DNA. 2-amino purine (2 AP) is incorporated in very small amount that it could not be possible to find out which base it replaces. 2, 6 diamino purine is highly mutagenic. 5-bromouracil can pair with adenine just like thymine (Fig. 40.17).

5-bromouracil (5-BU) and bromodeoxyuridine (BUdR) are analogues of thymine which are keto forms but can undergo tautomeric shifts they are enol form and pairs with Guanine (G) instead of Adenine (A) (Fig. 40.18). 5-BU produces G-C substitution for the original A-T, or it may occasionally be incorporated in the enol form as a pairing mate with guanine and then revert to its keto form to produce A-T substitution for the original G-C. Lawley and Brookes suggested that mispairing may be caused by ionization of bases rather than by tautomeric shifts. In this mechanism a base, e.g., 5-BU loses the hydrogen normally associated with its 3 nitrogen atom (Fig. 40.19 A, B).and may now pair with guanine (G).

The base analogue 2 amino purine (2 AP) shows mutational properties enabling it to be incorporated as a substitute of adenine but to pair subsequently with cytosine, or to pair initially with cytosine and subsequently with thymine. Incorporation a of AP at place of guanine (G) to give AP-C base pair will cause mutation in subsequent generation.

A mistake in replication after incorporation of 2-AP leads to the formation of AP-T base pair inducing transition.

Agents modifying purines and pyrmidines:

The agents which modify purines and pyrimidines or agents which stabilize the bases include nitrous oxide (HNO2), hydroxylamine and alkylating agents.

It reacts with bases containing amino groups. It changes the structure by deamination (removal of the amino group). The amino group (NH2) is replaced by hydroxyl group (OH – ). Nitrous acid deaminates, the bases, G, C and A with decreasing frequency. Deamination of adenine results in the formation of hypoxanthine (Fig. 40.20). Hypoxanthine pairs with cytosine instead of thymine. Thus A-T pairing is replaced by G-C pairs.

Deamination of cytosine at 6 position results in the formation of uracil (U) (Fig. 40.21) and the pairing of C-G instead of U-A is formed. Guanine deaminates to xanthine. Xanthine behaves like Guanine and pairs with cytosine, the pairing is X-C instead of G-C. Deamination of Guanine has no mutagenic affect (Fig. 40.22). The change in base pairing result in change in DNA in the 50% progeny. Deamination of gaunine, does not show any heritable mutation.

Table: 40.1. The structural and pairing behaviour change of DNA due to deamination by nitrous oxide:

Normal Base Normal pairing Deaminated Base New pair
Adenine A-T Hypoxanthine G-C
Cytosine C-G Uracil U-A
Guanine G-C Xanthine X-C

It reacts with cytosine and guanine, the hydroxylation of cytosine at amino group forms hydroxylcytosine which pairs with adenine because the hydroxyl amino group should be more electronegative than amino group. The hydroxylated molecule is in tautomeric form having a hydrogen atom in place of nitrogen at position 3. The effect of hydroxylamine on ‘C’ produces a transition in base pairing (Fig. 40.23)

Hydrazine (NH2NH2) breaks the rings of uracil and cytosine forms pyrazolone and 3-aminopyrasole. When DNA is treated with hydrazine it produces “apyrimidinic acid”. While when RNA is treated with hydrazine it produces “ribo-apyrimidinic acid”.

Many mutagenic agents carry one or more alkyl groups. These are called mono- , bi- or poly functional alkylating agents, e.g., dimethyl sulphate (DES), dimethyl sulphate (MMS), ethyl ethane sulphonate (DMS), methyl methane sulphonate (EES) and ehtyl methane sulphonate (EMS), etc. All of them act as mono-functional groups.

Agents producing distortion in DNA:

Proflavin and acridine orange are two important flourescent dyes which cause mutation by insertion or deletion of bases. Direct attachment of these dyes to the nucleic acid causes mutation.

Among the physical mutagens radiations are most important. They have direct effect on chromosome. They may break the chromosome directly or alter the DNA bases. If chromosomes at meiotic prophase are given radiation the frequency of mutant per viable organism increases linearly with the dose. Ressovsky et al (1935) suggested target theory stating that single hit of the particle (radiation) on the target (genetic material) inactivates or mutates it. The radiation may act through production of a chemical.

The frequency of simple chromosomal aberrations, e.g., deletion, is proposed to the dose of radiation (Fig. 40.24). Low O2 concentration reduces the frequency of chromosome breaks induced by radiations.

Oxygen effect is also called anoxia. Radiation in the presence of 02 forms some peroxide radicals which influence the frequency of breaks and mutations. Ionization of water in cells may give free radicals and hydrogen peroxide

The energy content of a radiation depends upon its wavelength. The shorter the wavelength the greater the energy value of a radiation. High energy radiations can change the atomic structure of a substance by causing the loss of an electron and the formation of an ion. Alternations in nucleic acid caused by radiation are of great importance. High energy ionizing radiations and ultraviolet light are mutagenic agents.

DNA and RNA absorbs UV light resulting in highly reactive free radicals in nitrogen containing bases. The unstability causes transition. If such changes occur in /w-RNA only few inactive proteins are formed in substitution in DNA have lasting effect producing defective protein. UV light produces thymine dimers (Fig. 40.25). 5, 6 unsaturated bonds of adjacent pyrimidines become covalently linked and form cyclobutance ring. Three possible types of pyrimidine dimers in DNA are found in irradiated bacterial culture.

In RNA pyrimidine dimers are formed between adjacent uracil and cytosine ring. These dimers cannot fit into the DNA double helix causing distortion of DNA molecules. If this damage is not repaired the replication is blocked and it is lethal. Exonuclease recognizes the distorted region and corrects it. DNA polymerase inserts correct bases in the gap and DNA ligases joins the inserted base.

UV radiation adds water molecules to pyrimidines in DNA as well as RNA resulting in photo hydrates (Fig. 40.26).

X-ray causes mutation by breaking the phosphates ester linkage in DNA at one or more points causing a large number of deletion of bases or rearrangement. In double stranded DNA breaks may occur in one or both the strands. If it is found in both the strands it is lethal. Sometimes two double stranded breaks may occur in the same molecule and the two broken ends may rejoin. The part of DNA between the two breaks is eliminated resulting in deletion.

UV induced mutation discovered by Kelner et al shows that UV effect can be reversed by exposing cells to visible light containing wave length in the blue region of spectrum. It is called photo reactivation. It was observed in bacteria and bacteriophages. It is caused by en2yme which splits thymine dimers and repair the DNA molecule. When DNA repair system is absent in humans xeroderma pigmentosum appears in the patients susceptible to sunlight.

What happens to the complementary base when the other undergoes a base substitution mutation? - Biology

There are many different ways that DNA can be changed, resulting in different types of mutation. Here is a quick summary of a few of these:

  1. change a codon to one that encodes a different amino acid and cause a small change in the protein produced. For example, sickle cell anemia is caused by a substitution in the beta-hemoglobin gene, which alters a single amino acid in the protein produced.
  2. change a codon to one that encodes the same amino acid and causes no change in the protein produced. These are called silent mutations.
  3. change an amino-acid-coding codon to a single "stop" codon and cause an incomplete protein. This can have serious effects since the incomplete protein probably won't function.

For example, consider the sentence, "The fat cat sat." Each word represents a codon. If we delete the first letter and parse the sentence in the same way, it doesn't make sense.

In frameshifts, a similar error occurs at the DNA level, causing the codons to be parsed incorrectly. This usually generates truncated proteins that are as useless as "hef atc ats at" is uninformative.

There are other types of mutations as well, but this short list should give you an idea of the possibilities.

7.5: DNA Lesions

  • Contributed by E. V. Wong
  • Axolotl Academica Publishing (Biology) at Axolotl Academica Publishing

The robust nature of DNA due to its complementary double strands has been noted several times already. We now consider in more detail the repair processes that rescue damaged DNA. DNA is not nearly as robust as popular media makes it out to be. In fact, to take the blockbuster book and film, Jurassic Park, as an example, Although there is unquestionably some DNA to be found either embedded in amber-bound parasites, or perhaps in preserved soft tissue (found deep in a fossilized femur, Schweitzer et al, 2007). It is likely to be heavily degraded, and accurate reproduction is impossible without many samples to work from.

The most common insult to the DNA of living organisms is depurination, in which the &beta-N-glycosidic bond between an adenine or guanine and the deoxyribose is hydrolyzed. In mammalian cells, it is estimated at nearly 10000 purines per cell generation, and generally, the average rate of loss at physiological pH and ionic strength, and at 37°C, is approximately 3 x 10 -11 /sec. Depyrimidination of cytosine and thymine residues can also occur, but do so at a much slower rate than depurination. Despite the high rate of loss of these bases, they are generally remediated easily by base excision repair (BER), which is discussed later in this section. Therefore it is rare for depurination or depyrimidination to lead to mutation.

Figure (PageIndex<15>). Depurination of guanines (or adenines) is a common DNA lesion.

Three of the four DNA bases, adenine, guanine, and cytosine, contain amine groups that can be lost in a variety of pH and temperature-dependent reactions that convert the bases to hypoxanthine, xanthine, and uracil, respectively. This can sometimes lead to permanent mutations since during replication, they serve as a template for the synthesis of a complementary strand, and where a guanine should go, for example (complementary to cytosine), an adenine may be inserted (because it complements uracil, the deamination product of cytosine).

Figure (PageIndex<16>)A. Deamination of adenine and guanine can lead to mutations upon replication if unrepaired.

Another deamination, of the modified base methylcytosine, can also lead to a mutation upon replication. Some cytosines may be methylated as part of a regulatory process to inactivate certain genes in eukaryotes, or in prokaryotes as protection against restriction endonucleases. When the methylated cytosine is deaminated, it produces a thymine, which changes the complementary nucleotide (upon replication) from a guanine to an adenine. Deamination of cytosines occurs at nearly the same rate as depurination, but deamination of other bases are not as pervasive: deamination of adenines, for example, is 50 times less likely than deamination of cytosine.

Figure (PageIndex<16>)B. Deamination of cytosine, and methylcytosine can lead to mutations upon replication if unrepaired.

Thymine good, Uracil bad. Why is thymine found in DNA rather than uracil? It turns out that the frequency of cytosine deamination may yield a clue as to why cells have gone the extra step (literally, since uracil is a precursor in thymine biosynthesis) to make a new &ldquostandard&rdquo nucleotide for DNA when uracil worked just fine for RNA, presumably the older genetic molecule. Consider this: if uracil was standard for DNA, then the very frequent deamination conversions of C to U would not be caught by error-checking for non-DNA bases, and the mutation rate would skyrocket. Fortunately, since T has evolved to be the standard base-pairing partner of adenine in DNA, uracil is quickly recognized and removed by multiple uracil DNA glycosylases (more on that later in this chapter), and the integrity of our DNA sequences is much safer.

All DNA bases can spontaneously shift to a tautomeric isomer (amino to imino, keto to enol, etc), although equilibrium leans heavily toward one than the other. When a rare tautomer occurs, it base-pairs differently than its more common structural form: guanines with thymines and adenines with cytosines. Here again, a mutation can be propagated during replication of the DNA.

DNA inside a cell must also contend with reactive oxidative species (ROS) generated by the cell&rsquos metabolic processes. These include singlet oxygen, peroxide and peroxide radicals, as well as hydroxyl radicals. although it is thought that the hydrogen peroxide and peroxide radicals do not directly attack the DNA but rather generate hydroxyl radicals that do. Most of these ROS are generated in the mitochondria during oxidative phosphorylation and leak out, although some may be generated in peroxisomes, or in some cytosolic reactions. Depending on what part of the DNA is targeted, ROS can cause a range of lesions including strand breaks and removal of bases.

Ionizing radiation (e.g. X-rays) and ultraviolet radiation can each cause DNA lesions. Ionizing radiation is often a cause for double-stranded breaks of the DNA. As described later in the chapter, the repair process for double-stranded breaks necessarily leads to some loss of information, and could potentially knock out a gene. Ultraviolet radiation that hits adjacent thymines can cause them to react and form a cyclobutyl (four carbons bonded in closed loop) thymine dimer. The dimer pulls each thymine towards the other, out of the normal alignment. Depending on the structural form of the dimer, this is sufficient to stymie the replication machine and halt replication. However, some data suggests that normal base-pairing to adenine may be possible under some conditions, although, it is likely only one base-pair would result, and the missing base could lead to either random substitution or a deletion in the newly synthesized strand.

Figure (PageIndex<17>). Ultraviolet radiation can be absorbed by some DNA and commonly causes pyrimidine cyclobutyl dimers connecting adjacent nucleotide bases.

Finally, we consider the formation of chemical adducts (covalently attached groups) on DNA. They may come from a variety of sources, including lipid oxidation, cigarette smoke, and fungal toxins. These adducts attach to the DNA in different ways, so there are a variety of different effects from the adducts as well. Some may be very small adducts - many environmental carcinogens are alkylating agents, transferring methyl groups or other small alkyl groups to the DNA. Other adducts are larger, but also attach covalently to a nitrogenous base of DNA. Common examples are benzo(a)pyrene, a major mutagenic component of cigarette smoke, and aflatoxin B1, produced by a variety of Aspergillus-family fungi. Benzo(a)pyrene is converted to benzo(a)pyrene diol epoxide, which can then attack the DNA. When this happens, the at pyrene ring intercalates between bases, causing steric changes that lead to local deformation of the DNA and disruption of normal DNA replication.

Figure (PageIndex<18>). Benzo(a)pyrene is converted to an epoxide form by the cell. The epoxide can form an adduct on DNA.

Aflatoxin B1 is the primary aflatoxin produced by some species (esp. flavus, parasiticus) of Aspergillus, a very common mold that grows on stored grain (as well as detritus and other dead or dying plant matter). In addition to infecting grain, it is a common problem with stored peanuts. At high levels, aflatoxin is acutely toxic, but at lower levels, it has the insidious property of being unnoticeably toxic but mutagenic. Like benzo(a) pyrene, it is metabolized into an epoxide and will then react with DNA to form an adduct that can disrupt replication.

Figure (PageIndex<19>). The epoxide form of aflatoxin also forms adducts on DNA.

Some alkylating agents, particularly N-nitroso compounds, are formed in the acidic conditions of the stomach from nitrosation of naturally occurring nitrites produced from food (reduction of nitrates), or environmental nitrites in drinking water. Ironically, while some alkylating agents can cause cancers, others are used therapeutically as anticancer treatments, e.g. mitomycin, melphalan. The idea, as with many cancer treatments, is that although such drugs cause DNA damage to non-cancerous cells as well as cancer cells, the high rate of cancer cell proliferation gives them fewer chances for repair of damaged DNA, and thus greater likelihood that the damage might halt replication and lead to cell death.

In a similar vein, crosslinking chemotherapeutic agents such as cisplatin (a platinum atom bonded to two chloride groups and two amino groups) also bind to DNA. The chloride groups are displaced first by water and then by other groups including sites on DNA. Although sometimes classified as an alkylating agent, it obviously is not, but it acts similarly. Cisplatin goes a step further than a simple alkylating agent though, because it has another reactive site and can thus crosslink (covalently bond) another nucleotide, possibly on another strand of DNA, making a strong obstruction to DNA replication. Cisplatin can also crosslink proteins to DNA.

Benzo(a)pyrene and aflatoxin B1 are not themselves mutagens. Once they are in the cell, the normal metabolism of these compounds leads to diol epoxide formation, which can then attack the DNA. Although the 7-nitrogen (N7) of guanine is more nucleophilic, and is a target for aflatoxin, most benzo(a)pyrene diol epoxide adducts attach to the 2-nitrogen of guanine residues.

There are federal standards (20-300 parts per billion depending on usage) for aflatoxin in various forms of grain-based animal feed, especially corn-based feeds, because the toxin can pass through the animal into milk, as well as linger in the meat. In addition to feed, there are federal maximums for peanuts and peanut products, brazil nuts, pistachios, and other foodstuffs (actionable at 20 ppb).

Well then, what&rsquos a poor cell to do when its DNA is being constantly ravaged? As it turns out, there are some very good repair processes that are constantly at work on the DNA, scanning it for defects, and where possible, making repairs. Often the repairs are perfect, if the complementary strand is intact, sometimes mutations must be introduced, and finally there are occasions when repair is impossible, and apoptosis is triggered to kill the cell and prevent propagation of damaged DNA.

Watch the video: Νεκρή από κορωνοϊό 27χρονη στη Θεσσαλονίκη. Κεντρικό Δελτίο Ειδήσεων 6112021. OPEN TV (May 2022).