Gene and DNA Mutations: How Do Cells Repair Genetic Mutations ?

How are DNA Mutations Caused?

We don’t live in a ideal world. As a result, any life system that wishes to survive under less than ideal conditions has to develop its own capacity to overcome the hurdles it faces. Similarly, the living cell as an independent entity is being bombarded with harmful radiation from the sun, chemical carcinogens from the environment, in addition to other harmful environmental factors too numerous to list here. Therefore, it has to have a robust system in order to tackle the damage that happens to the genetic information molecule, e.g., the DNA. Any mutations that happen to the DNA would then be propagated in further downstream processes. Mutations that occur naturally are termed spontaneous mutations and take place on a continual basis, and a second category of mutations is induced mutations. These mutations are responsible for evolutionary advances, but they can also be harmful.

Genetic Mutation Repair Mechanisms

Since the possibility of avoiding mutations is not easily accomplished, the second best strategy is to fix those mutations. A whole set of proteins are involved in what is known as the DNA repair machinery pathway. This pathway fixes any errors and defects in the DNA sequence. This pathway involves several proteins that are significant to the cell’s survival, just as they are responsible for fixing the mutation in the DNA sequence. Since damage to DNA involves several parameters apart from just a mutation, there are multiple mechanisms at work here to deal with each and every type of DNA damage. Different types of damage to DNA may include single strand breaks, formation of adducts by exposure to harmful radiation, and so on.

Types of Repair Mechanisms

Base excision:

Involves the removal of a particular damaged nucleotide base from the DNA sequence. The damaged base is first marked chemically for removal, then is later excised out from the sequence by an enzyme called DNA glycosylase. The region is acted upon by another enzyme that removes further bases above and below region of interest. Later, the DNA polymerase resynthesizes the nucleotides which are then ligated by the enzyme called ligase.

Nucleotide excision:

The nucleotide excision system positions itself at the region of the genetic mutation or defect and it then cuts a set of nucletoides from the DNA sequence on either side of the mutation. Once this is completed, the DNA polymerase moves in to synthesize the region that is lost and then ligase takes care of incorporating the synthesized region into the DNA strand.

Mismatch Repair:

Mismatch repair mechanisms kick in when the base pairing rule is violated and bases are paired improperly. In this case the decision as to which base is the legitimate one is done by looking for a chemical modification called "methylation" which is done only to the template strand of the DNA from the child strand replicates. Once the correct base has been determined, the whole region of nucleotides from the region at the methylation mark to the region of mismatch are removed. DNA polymerase aids in resynthesizing the strand.

Suggested Reading:

Cellular machinaries for chromosomal DNA repair,Genes & Development, 2004.