Mutation: Nature, Repair and Recombination

DNA mutations are sudden or random alterations in the gene or chromosomal structure or number, leading to genotypic or phenotypic change. The mutation can occur at a single nucleotide base known as a point mutation or multiple genes. DNA repair is a process which identifies the damage or error in the DNA molecule and corrects it. DNA damage occurs in human cells leading to the occurrence of DNA lesions. Most lesions cause structural damage to the DNA molecule and alter the cell’s ability to transcribe the gene encoded by the affected DNA. DNA repair is an active mechanism which makes necessary repairs and responds to damage to DNA structure. 

Different Types of DNA Damage  

DNA damage and mutation are caused due to many factors. Constant exposure to genotoxic components causes DNA lesions that block genomic replication and transcription. The DNA damage or mutation of the nucleotide base or chromosome leads to double-strand breaks and mutations.

• Point Mutations – These are the simplest types of mutations where one nucleotide base is replaced with another. The point mutations are silent, which does not change the amino acid. The missense mutation leads to the formation of entirely different amino acids. A nonsense mutation is when the substitution of a single nucleotide leads to the formation of a stop codon. 
• Substitution – This is of two types which are transition and transversion. Transition mutation is when another pyrimidine substitutes one pyrimidine or replaces purine with another purine. Transversion involves the substitution of pyrimidine for purine and vice versa. 
• Deamination – This type of mutation leads to cytosine deamination to form uracil that base pairs with adenine instead of guanine in the next replication cycle. Hence, the C-G pair is replaced by T-A in the next replication cycle. 
• Chemical modification of nucleotide base – Whenever there is a chemical modification in any of the four bases of the DNA, it leads to a modification. For example, one modification is adding a methyl group to the nucleotide base forming 7-methylguanine, 3-methyladenine, 5-methylcytosine etc. 
• Formation of Pyrimidine Dimers – One of the common types of mutation is the thymine dimers, which form a covalent bond (cyclobutyl ring) between adjacent thymine bases. 
• Strand breaks – Various chemicals cause the break in the phosphodiester bond in the DNA strand like radiations, peroxides, enzymes like DNase etc. This leads to DNA backbone breakage. 

DNA Repair Mechanisms 

A DNA repair mechanism rectifies the errors that occur during the DNA replication process. DNA repair is a process in which a cell identifies the damage in the DNA and corrects it to prevent DNA lesions and mutations. There are many factors which impact the rate of DNA repairs like cell type, age of the cell, and extracellular environment. 

Excision Repair

• The primary DNA repair mechanism helps repair the damage by excising the nucleotides bases when there is an error. 
• The base excision repair is the removal of a damaged nucleotide base. The repair is done by hydrolyzing the glycosidic bonds. 
• Nucleotide excision repair targets DNA double helix distortion or distortion due to the addition of large chemicals to the bases. 
• The nucleotide repair system includes three steps which are incision, excision, and synthesis. The endonuclease enzyme does the incision. 

Direct Repair: 

• This type of repair is known as photoreactivation, as the repair enzyme reverses the damage. It is done in the presence of a light-dependent enzyme DNA photolyase. The enzyme is present in all cells, and it uses energy from the absorbed light to cleave the C-C bond of the cyclobutyl ring of thymine dimers.  

Mismatch Base Repair: 

• Wrong bases are incorporated into the daughter strand during the replication process. Hence, for distinguishing the two strands for repair purposes, the adenine base of the template strand is tagged by methyl groups. The newly replicated DNA helix is hemimethylated. This repair involves the excision of the wrong bases in the daughter strand.  

Recombination Repair System 

• The recombination mechanism repairs the gap in the newly synthesised daughter strand. In this recombination repair system, a short identical segment of DNA is retrieved and inserted into the gap. Hence, in such repair, a portion of the DNA strand is retrieved from the normal homologous DNA segment. 
• The homologous recombination repair system is also known as double-strand breakage repair. In this type of recombination repair, a template of an undamaged DNA single strand is used to finish the resynthesis of damaged DNA. 
• It includes SOS Repair, a repair mechanism required when cells are in a critical state due to severe DNA damage. At times, replicating machinery cannot repair the damaged portion and bypass the damaged site. This requires an emergency repair system. Hence, the SOS repair mechanism is catalysed by a special class of DNA polymerase known as the Y-family of DNA polymerase. This synthesises DNA directly across the damaged part of the DNA. 

Conclusion 

Many sources lead to DNA damage and mutations, but the body has its repair mechanism to prevent the damage and correct the error. DNA repair and resynthesis of the damaged strand are necessary to repair the DNA damage. There are different types of DNA damage like point mutation (single nucleotide base change), substitution mutation, deamination, chemical modification, pyrimidine dimers, and strand breaks. However, the body has its repair and recombination mechanism, which helps prevent such errors from occurring.