Understanding Nucleotide Excision Repair Steps

Nucleotide Excision Repair (NER) is a crucial cellular mechanism that removes bulky, helix-distorting DNA lesions, such as those caused by UV radiation or chemical mutagens. The process involves several key steps to accurately restore the DNA sequence.

Step 1: DNA Unwinding (C)

The initial step in NER involves the recognition of the DNA damage. Following recognition, the DNA double helix is unwound around the damaged site. This unwinding creates a localized "bubble" or open region, allowing access for repair enzymes to the damaged bases.

Corresponding letter: C. The DNA is unwound producing a "bubble".

Step 2: Incisions by Endonucleases (B)

Once the DNA is unwound and the damaged segment is accessible, specific enzymes called endonucleases are recruited. These enzymes make precise cuts in the phosphodiester backbone of the DNA strand. Importantly, cuts are made on both the 3' side and the 5' side of the damaged region, flanking the lesion.

Corresponding letter: B. Cuts are made on both the 3' side and the 5' side of the damaged area.

Step 3: DNA Synthesis (A)

After the damaged fragment is excised (removed), the resulting gap needs to be filled. A DNA polymerase enzyme synthesizes a new segment of DNA. This synthesis uses the undamaged complementary strand as a template, ensuring the correct sequence is restored. This is often described as a "fresh burst" of DNA synthesis.

Corresponding letter: A. A fresh burst of DNA synthesis.

Step 4: Ligation (D)

The final step in the NER pathway involves sealing the newly synthesized DNA segment into the existing DNA backbone. This is accomplished by the enzyme DNA ligase. DNA ligase forms a phosphodiester bond, covalently linking the 3' end of the newly synthesized DNA to the 5' end of the preceding DNA segment, thus completing the repair process.

Corresponding letter: D. A DNA ligase covalent binds the fresh piece into the backbone.

Correct Sequence

Based on the steps described, the correct order of events in nucleotide excision repair is C, B, A, D.

• C: DNA unwinding to create a bubble.
• B: Endonucleases make cuts on both 3' and 5' sides.
• A: DNA polymerase synthesizes new DNA.
• D: DNA ligase seals the nick.