Common Systems for Direct DNA Repair

The process follows a highly regulated sequence:

1. Recognition and Removal: An enzyme called DNA $N$-glycosylase identifies the specific damaged base and cleaves the bond between the base and the sugar-phosphate backbone. This leaves behind an AP (apurinic/apyrimidinic) site, also known as an "abasic site".
2. Incision: An AP endonuclease recognizes this empty site and cuts the DNA backbone near the lesion, creating a "nick".
3. Synthesis and Ligation: Through a process known as nick translation, DNA polymerase removes the incorrect segment and synthesizes new, correct nucleotides using the undamaged complementary strand as a template. Finally, DNA ligase seals the remaining nick in the backbone to restore a continuous strand.

Nucleotide Excision Repair (NER)

While BER handles small, single-base lesions, Nucleotide Excision Repair (NER) is designed to handle much larger, "bulky" distortions in the DNA double helix, such as those caused by UV-induced photoproducts. Because it can handle a wider variety of lesions, NER is a nearly universal mechanism found in almost all bacteria and eukaryotes, including humans.

In bacteria, NER is mediated by a specific set of UV repair genes known as the uvr genes. The mechanism functions as follows:

• Detection: The UVR A and UVR B proteins scan the DNA to identify structural distortions.
• Cleavage: Once the damage is found, UVR C acts as an endonuclease to cleave the DNA strand on both sides of the lesion.
• Excision: UVR D, a DNA helicase, assists in unwinding the DNA to release the damaged single-stranded fragment, which is typically about 12 nucleotides long.
• Gap Filling: Much like in BER, DNA polymerase fills the resulting gap using the intact strand as a guide, and DNA ligase seals the final break.

Mismatch Repair (MMR)

Even with high-fidelity DNA polymerases, errors occasionally occur during DNA replication, such as the incorporation of a non-complementary base (e.g., a G paired with a T). This is known as a mismatch.

Mismatch Repair (MMR) is the system dedicated to correcting these errors. The primary challenge for the MMR system is distinguishing between the "old" (correct) template strand and the "new" (erroneous) strand. Once the mismatch is identified, the system excises a segment of the newly synthesized strand containing the error. DNA polymerase then resynthesizes the sequence, and DNA ligase completes the repair to ensure the double helix is perfectly matched.

💡 Exam Tip: Comparing BER and NER

If a question asks which repair system handles a single damaged base (like a uracil), the answer is Base Excision Repair (BER). If the question describes a bulky lesion or a large segment of nucleotides being removed (like a thymine dimer), the answer is Nucleotide Excision Repair (NER).

Summary Table of Repair Mechanisms