Nucleotide excision repair

Definition

Nucleotide excision repair (NER) is a critical DNA repair mechanism that removes damaged DNA segments and synthesizes new DNA to replace them. This process is vital for maintaining genomic integrity, especially when cells face harmful agents like UV radiation or chemical mutagens that can distort the DNA structure. NER operates through a series of coordinated steps, ensuring that bulky DNA lesions are efficiently recognized and repaired, thereby preventing potential mutations and maintaining normal cellular function.

5 Must Know Facts For Your Next Test

1. Nucleotide excision repair is responsible for removing a wide range of DNA lesions, particularly those caused by UV light, such as thymine dimers.
2. The NER process involves recognizing the distortion in the DNA helix caused by damage, excising the damaged section, and synthesizing new DNA to fill in the gap.
3. There are two main sub-pathways of NER: global genome NER, which scans the entire genome for damage, and transcription-coupled NER, which prioritizes genes that are being actively transcribed.
4. Defects in nucleotide excision repair are linked to several genetic disorders, including Xeroderma pigmentosum, which results in extreme sensitivity to sunlight and a predisposition to skin cancers.
5. The key proteins involved in NER include XPC, which recognizes DNA damage, and XPB and XPD helicases that unwind the DNA during repair.

Review Questions

• How does nucleotide excision repair distinguish between damaged and undamaged DNA strands?
  • Nucleotide excision repair distinguishes between damaged and undamaged strands primarily by recognizing distortions in the DNA helix. The protein complex XPC is crucial for sensing these structural changes. Once damage is identified, the repair machinery is recruited to remove the damaged section from the strand. This selective action ensures that only the necessary portions of DNA are modified while preserving the integrity of undamaged sequences.
• Discuss the significance of transcription-coupled repair within the broader framework of nucleotide excision repair.
  • Transcription-coupled repair (TCR) is significant because it ensures that actively expressed genes are prioritized for repair. TCR specifically targets lesions on the strand of DNA being used as a template for RNA synthesis. This mechanism allows cells to quickly restore functional genes, thus maintaining essential cellular processes and overall gene expression levels. By having this specialized pathway alongside global genome NER, cells can efficiently manage damage while ensuring critical functions remain intact.
• Evaluate how defects in nucleotide excision repair can lead to increased cancer susceptibility and relate this to its biological functions.
  • Defects in nucleotide excision repair can significantly elevate cancer susceptibility due to the accumulation of unrepaired DNA damage. For instance, individuals with Xeroderma pigmentosum suffer from a genetic inability to perform effective NER; as a result, they exhibit heightened sensitivity to UV radiation and an increased risk of skin cancers. The biological function of NER is crucial for correcting harmful alterations in DNA. When this system fails, it leads to mutations that can propagate through cell divisions, ultimately contributing to tumorigenesis and other severe health issues.

Related terms

DNA damage: Changes to the chemical structure of DNA that can lead to mutations, which may result from environmental factors or errors during DNA replication.

repair pathways: Biochemical processes that cells utilize to fix various types of DNA damage, including base excision repair, mismatch repair, and nucleotide excision repair.

transcription-coupled repair: A sub-pathway of nucleotide excision repair that specifically targets lesions on the actively transcribed strand of DNA, ensuring that essential genes are expressed correctly.