Toxicology

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Base excision repair

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Toxicology

Definition

Base excision repair is a cellular mechanism that fixes small-scale DNA damage, specifically damaged or non-canonical bases. This process is crucial for maintaining genetic stability, as it recognizes and removes aberrant bases, replacing them with the correct nucleotides to ensure the integrity of the DNA sequence.

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5 Must Know Facts For Your Next Test

  1. Base excision repair is primarily responsible for fixing oxidative damage, alkylation damage, and deamination of bases, which can occur due to environmental factors or metabolic processes.
  2. The process begins when DNA glycosylases identify and remove the damaged base, resulting in an abasic site that is then processed by other enzymes.
  3. Following the removal of the damaged base, an endonuclease cuts the DNA backbone at the abasic site, allowing for subsequent steps to fill in the gap with the correct nucleotide.
  4. Base excision repair is essential for preventing mutations that could lead to diseases such as cancer, highlighting its role in genomic stability.
  5. Deficiencies in base excision repair pathways can result in increased sensitivity to DNA-damaging agents and contribute to various genetic disorders.

Review Questions

  • How does base excision repair identify and process damaged DNA bases?
    • Base excision repair identifies damaged DNA bases through the action of specific enzymes called DNA glycosylases. These enzymes recognize non-canonical bases or modified nucleotides and remove them, creating an abasic site. This site is then processed by endonucleases and other enzymes to ensure the correct nucleotide is inserted, restoring the integrity of the DNA strand.
  • Discuss the importance of base excision repair in maintaining genomic stability and its implications for health.
    • Base excision repair is vital for maintaining genomic stability as it repairs small-scale DNA damage that can lead to mutations if left unaddressed. By correcting oxidative damage and other modifications, this repair mechanism helps prevent diseases such as cancer. A failure in this system can result in accumulated mutations and increased susceptibility to DNA-damaging agents, ultimately affecting overall health.
  • Evaluate how defects in base excision repair might influence cancer development and treatment responses.
    • Defects in base excision repair can significantly influence cancer development by allowing mutations to accumulate within critical genes that regulate cell growth and apoptosis. This accumulation increases the risk of oncogenesis as cells may become more genetically unstable. Furthermore, tumors with deficient base excision repair pathways may exhibit altered responses to certain chemotherapeutic agents, particularly those that induce DNA damage, impacting treatment efficacy and patient outcomes.
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