7.4
Nucleotide Excision Repair
Exposure to mutagens can damage DNA and result in bulky lesions that distort the double-helix structure or impede proper transcription. Damaged DNA ca…
Nucleotide excision repair, or NER, fixes bulky DNA lesions caused by UV radiation and chemical carcinogens.
These bulky lesions, such as pyrimidine dimers, distort the DNA helix and interfere with DNA replication and transcription.
In the bacterium E. coli, the repair proteins UvrA and UvrB form a complex that scans genomic DNA for structural lesions.
Once the complex encounters a lesion, UvrA dissociates, causing UvrB to bind tightly to the distorted DNA.
The DNA-bound UvrB then recruits UvrC, an endonuclease, which makes incisions on either side of the lesion.
Next, the UvrD helicase unwinds the DNA and releases the fragment carrying the lesion.
Following excision, DNA polymerase fills the gap with new complementary nucleotides. DNA ligase then seals the gap between the new and old DNA, completing the repair.
Alternatively, if an actively transcribing RNA polymerase stalls at a bulky lesion, the stalled complex promotes recruitment of the UvrA–UvrB repair machinery to the site.
This initiates transcription-coupled nucleotide excision repair, which proceeds in the same manner as regular NER and allows transcription to continue.
Q1: What is nucleotide excision repair and why is it important?
Nucleotide excision repair (NER) is a DNA repair mechanism that removes and replaces damaged nucleotides caused by UV radiation and chemical mutagens. This process is critical for maintaining genome stability and preventing mutations that could lead to cancer or cell death. NER protects cells from environmental DNA damage by recognizing distortions in the DNA helix and excising the damaged region.
Q2: How do repair proteins recognize DNA damage in nucleotide excision repair?
Repair proteins detect DNA damage through recognition of helix distortions caused by lesions. These proteins scan the DNA and identify abnormal structural changes rather than specific chemical modifications. Once damage is recognized, the repair machinery is recruited to the site to begin the excision and replacement process.
Q3: What happens during the excision of damaged nucleotides?
During excision, repair enzymes make cuts on both sides of the damaged DNA lesion, removing a segment containing the injury. The excised oligonucleotide is then replaced with newly synthesized DNA using the undamaged complementary strand as a template. This restoration process restores the original DNA sequence and function.
Q4: Which types of DNA damage does nucleotide excision repair target?
Nucleotide excision repair primarily targets bulky DNA lesions that distort the DNA helix, including UV-induced thymine dimers and adducts from chemical mutagens. These lesions create structural abnormalities that trigger NER recognition. The mechanism is particularly effective against environmental and chemical DNA damage.
Q5: How does nucleotide excision repair differ from other DNA repair pathways?
Unlike base excision repair, which targets small lesions, nucleotide excision repair removes larger damaged segments and is triggered by helix distortion rather than specific base modifications. NER is also distinct from homologous recombination and strand invasion mechanisms, which address different types of DNA damage like double-strand breaks.
Q6: What role does nucleotide excision repair play in preventing mutations?
By removing and replacing damaged nucleotides before DNA replication, nucleotide excision repair prevents error-prone polymerases from incorporating incorrect bases opposite lesions. This proactive removal of damage maintains genetic fidelity and reduces mutation rates. Defects in NER genes are associated with increased cancer susceptibility.
Q7: How does UV radiation trigger nucleotide excision repair?
UV radiation creates thymine dimers and other photoproducts that distort the DNA helix structure. These structural abnormalities are recognized by NER surveillance proteins, which initiate the repair cascade. The helix distortion serves as the primary signal for recruiting repair machinery to damaged sites.