Overview of DNA Repair

As the repository of all genetic information, DNA is highly stable. 

However, like any organic molecule, it is susceptible to a variety of changes that alter its base chemistry including heat, radiation, and oxidation by free radicals produced during cellular respiration.

Also present abundantly in the cell is water, and this can cause hydrolytic damage. There are two types of hydrolytic reactions that spontaneously damage DNA bases under physiological conditions. 

The first, deamination, affects pyrimidine bases such as cytosine, and is defined by the loss of an amino group in the presence of water that converts the base into Uracil. The second is depurination, which is the loss of purine bases due to the cleavage of the bond between the base and deoxyribose - leaving an apurinic site in the DNA.

These different types of damage lead to random mutations, which can be very harmful, causing genome instability, cell death, or cancers, amongst other conditions. Thankfully, only a few of these mutations are retained during DNA replication due to the cell’s highly efficient repair mechanisms.

The double-stranded structure of DNA itself is particularly suitable for repair because it contains two separate copies of the genetic information in its two strands. This means that, when one strand is damaged, the complementary strand can be used as a template to restore the correct nucleotide sequence.

There are three common DNA repair mechanisms. The first, base excision repair, focuses on fixing endogenous DNA damage, such as the hydrolytic damage resulting in deamination or depurination. Nucleotide excision repair can fix damage caused by ultraviolet light or certain chemical carcinogens, and finally, mismatch repair fixes faulty base incorporation by DNA polymerase during replication which leads to incorrect base-pairing.