The Science of DNA Repair

DNA repair is a crucial process that corrects damaged or erroneous DNA sequences to maintain the integrity of the genetic material. There are several mechanisms of DNA repair, and two important ones are base excision repair (BER) and SOS repair.

The processes are detailed here.

Base Excision Repair (BER)

Base excision repair is a highly conserved and prevalent DNA repair pathway that primarily deals with the repair of damaged or modified bases. It corrects small, non-bulky lesions such as oxidized, deaminated, or alkylated bases.The steps involved in base excision repair are as follows:

Step 1: Recognition and Removal of the Damaged Base Specific DNA glycosylases recognize and bind to the damaged base, causing it to flip out of the DNA helix. The glycosylase then cleaves the glycosidic bond between the damaged base and the sugar-phosphate backbone, resulting in the removal of the damaged base and the creation of an apurinic/apyrimidinic (AP) site.

Step 2: AP Site Processing An AP endonuclease or AP lyase recognizes the AP site and cleaves the DNA backbone at the site of the missing base. This generates a DNA strand break with a 3′-hydroxyl group and a 5′-deoxyribose phosphate (dRP) group.

Step 3: Gap Filling and Ligation DNA polymerase β (pol β) binds to the 3′-hydroxyl group generated in the previous step and extends the DNA chain by adding the correct nucleotides in a template-dependent manner. The dRP group is simultaneously removed by the action of a dRPase enzyme. Finally, DNA ligase seals the nick, completing the repair process.

Base excision repair is a relatively fast and efficient repair mechanism that deals with a wide range of DNA lesions. However, it is limited to the repair of single-base damage and cannot address more complex DNA lesions.

SOS Repair

SOS repair is a DNA repair system that operates in bacteria and is activated under conditions of severe DNA damage or replication stress. It is an error-prone repair mechanism that allows for the replication and survival of damaged DNA, even if it introduces mutations.The steps involved in SOS repair are as follows:

Step 1: Activation of the SOS Response.

Severe DNA damage or stalled replication forks trigger the activation of the SOS response. This is mediated by a regulatory protein called RecA, which undergoes a conformational change upon binding to single-stranded DNA (ssDNA) produced during DNA damage.

Step 2: RecA-Mediated Proteolytic Cleavage of LexA Repressor

Activated RecA promotes the self-cleavage of the LexA repressor protein, which is responsible for inhibiting genes involved in DNA repair and mutagenesis. The cleavage of LexA derepresses these genes, allowing them to be expressed.

Step 3: Induction of DNA Repair and Mutagenesis Genes

The derepressed genes, including those encoding DNA polymerases with low fidelity (such as Pol IV and Pol V), are expressed. These polymerases can bypass damaged DNA sites and introduce mutations, but they allow for continued replication and survival.

SOS repair is considered a last-ditch effort to rescue damaged DNA. It sacrifices accuracy for the sake of cell survival by allowing replication to continue even with potentially mutagenic lesions. However, it increases the risk of introducing errors into the genome.

Overall, base excision repair and SOS repair are two important mechanisms that play distinct roles in the repair of damaged DNA. Base excision repair is a precise and efficient pathway involved in the repair of small, non-bulky lesions, while SOS repair is an error-prone mechanism activated under severe DNA damage conditions to allow replication and survival at the cost of increased mutagenesis.