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DNA Damage and Types of Mutation

BY: Lakshmi K Sugavanam | Category: DNA | Submitted: 2011-04-20 08:14:07
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Article Summary: "Although DNA is usually copied faithfully through replication process, sometimes one to many bases can be changed or deleted, thus damaging the DNA and the integrity of the information it carries..."

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DNA is the carrier of genetic material and has to be passed on from generation to generation without any errors. It has to be replicated and passed on into new cells accurately for the progeny to resemble the parent cells. Although this process generally occurs perfectly, there are chances for errors to occur. It is estimated that when replication occurs, there may occur one error per billion base pairs. However, the cells are usually able to repair the damage through the various repair mechanisms.

In some cases, the repair that occurs during replication may accumulate to result in mutations. There is an estimate that for every 106 base pairs in the genome, there will be present one mutation. Other than replication errors, chemical and physical agents can also cause DNA damage. These agents can include free radicals, chemicals, radiation etc. and the damages brought upon by them may result in mutations. However, it is found that these may occur at sites other than those that are responsible for coding proteins and hence, may not impact the organism in anyway. But, if they do happen to occur at sites that are responsible for the coding, they may be responsible for some serious condition.

The types of DNA damage may be classified into four categories:
• Single-base alterations-depurination, deamination
• Two-base alterations- pyrimidines diamer
• Chain breaks- ionizing radiation
• Cross-linkages- between bases

Spontaneous deamination of some bases may occur. For example, cytosine may get deaminated to form uracil spontaneously; adenine, forms hypoxanthine. Spontaneous depurination can also occur due to the cleavage of the glycosyl bonds connecting purine to the backbone. These sites are called as apurinic sites which indicate the absence of purine or DNA at that site. Some of these base alterations can cause the formation of reactive oxygen species that is commonly called as free radicals. These can be responsible for DNA damage and this phenomenon can increase with age.

Radiations like ultraviolet radiations and X-rays can also cause DNA damage. UV radiations can cause the formation of covalent bonds to form between pyrimidines bases, resulting in pyrimidines dimmers. X-rays are ionizing radiations that can cause breaks in the DNA.

Although the DNA is generally stable, it may undergo gradual changes over a period of time. When there is a change in the structure of the DNA that makes up a gene, it is called as a mutation. The agent that introduces the change is called the mutagen. The effect of the mutation may be expressed in the replication stage, the transcription stage or the translation stage.

Mutation can be of two main types- point mutation or frameshift mutation. Point mutations are those in which one base pair is replaced by another. They, in turn, can be of two types- transitions or transversions. If a purine is replaced by a purine or a pyrimidine by a pyrimidines, such a point mutation is called a transition. If a purine is replaced by a pyrimidines or a pyrimidines by a purine, it is called as transversion. A frameshift mutation is one in which one more base pairs are either inserted or deleted from the DNA strand.

A point mutation can be significant in that a base change can cause a
-Silent Mutation: Sometimes, even though a mutation has occurred in the DNA, the mRNA may still code for the correct protein. This may occur due to the degeneracy of the code. Since the same amino acid is coded for, the mutation goes undetected and hence the name.
-Nonsense mutation: A change in a base may result in the formation of a termination codon or a stop codon. This puts a stop to the protein synthesis.
-Missense mutation: A change in base can result in a codon for a different amino acid which may or may not be appropriate for the protein molecule to function.

A frameshift mutation can have a great impact on the protein being produced as the insertion or deletion of a base can alter the reading frame of the entire DNA that follows. The wrong amino acids and consequently the wrong protein may be produced.

It is believed that mutations are responsible for a range of diseases and afflictions. Sickle cell anemia is an example of a missense mutation where GAG coding for glutamic acid is changed to GUG coding for valine. Mutations may also be responsible for some types of cancers.

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