Gene Mutation and DNA repair
Mutation can happen during the recombination or replication. It is the permanent change that happens to the sequence of the DNA in the nucleotide. The cause of mutation within the DNA can be due to insertion of base pair, deletion or substitution.
Mutations are not harmful until they cause a tumor or cell death. The fatal outcomes of the gene mutation are the reason that DAN repair is important. Before understanding DNA repair, it is important that we understand the causes of gene mutation.
Causes of gene mutation
1-Error in DNA replication
Rarely the DNA polymerase will cause the attachment of the noncomplementary base in the strand. In the next round of replication, this base would lead to mutation. It happens rarely because the exonuclease will work as the proofreading mechanism and it will remove all the mismatched base pairs.
2-Error in DNA recombination
Recombination is the process in which the DNA will rearrange its strands. In this process, the DNA is often lost that leads to mutation.
There are many radioactive chemicals that are produced in the industries, from the lands and laboratories. Their rays can cause serious mutation in the genes if they are absorbed excessively.
Different methods are used to repair the damaged DNA.
During the strand synthesis, an incorrect nucleotide is incorporated by the DNA polymerase and it changes the 3′ to 5′ strand and the exonuclease cannot correct it. It can be repaired with the mismatch repair mechanism.
The mechanism relies on the secondary signals sent by the DNA that helps to distinguish the parent and daughter strand and helps in the identification of the replication error. There is a mismatch repair system in humans.
- On both strands, Methylation will happen with the sequence of GATC after replication.
- The daughter strand will be unmethylated because DNA strands are semi-conservative for a limited time
- It will help the mismatch mechanism to find the error in the strand.
- The bands in the mismatched pairs will be recognized by the MutS protein.
- MutL will bind with the MutS and MutH will bind with the methylated sequence GATC.
- MutL/MutS complex will link with MutH and will cut off the unmethylated strand at the site of GATC
- Now MutU, DNA Helicase will unwind the DNA strand to remove the error in the strand
- If the DNA is not repaired it might lead to colorectal cancer in humans.
Nucleotide Excision Repair
The formation of the complex proteins like HSSB, ERCC1, XPF and XPA at the lesion of the DNA starts the NER process. To make an incision the transcription factor TFIIH will bind with the ATP complex. The 29 nucleotide of the damaged DNA will be unwound and the mutation is removed. Ligase will seal the DNA strands again.
There are specialized enzymes in the human body will help to repair the damaged DNA directly. Sometimes the cells are replicated to get rid of the damaged part of the DNA.