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8-oxoguanine

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Biological Chemistry I

Definition

8-oxoguanine is a modified form of the DNA base guanine that results from oxidative stress, where oxygen species react with guanine, leading to potential mutations. This altered base can mispair with adenine during DNA replication, increasing the risk of genetic mutations and contributing to various diseases, including cancer. It is a significant marker for oxidative DNA damage, highlighting the importance of DNA repair mechanisms in maintaining genetic integrity.

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5 Must Know Facts For Your Next Test

  1. 8-oxoguanine is formed primarily through the oxidation of guanine, making it one of the most common forms of oxidative DNA damage.
  2. If not repaired, 8-oxoguanine can lead to G:C to T:A transversions during DNA replication, which can initiate mutagenesis.
  3. Cells utilize specialized glycosylases such as OGG1 (8-oxoguanine glycosylase) to recognize and excise 8-oxoguanine from DNA.
  4. High levels of 8-oxoguanine have been associated with aging and a variety of age-related diseases, indicating its relevance in cellular aging.
  5. Detection of 8-oxoguanine is often used as a biomarker for oxidative stress and the effectiveness of antioxidant therapies.

Review Questions

  • How does 8-oxoguanine impact DNA replication and what consequences does this have for genetic stability?
    • 8-oxoguanine can mispair with adenine during DNA replication, resulting in G:C to T:A transversions. This mispairing can lead to permanent mutations if not corrected by repair mechanisms. The accumulation of these mutations can compromise genetic stability and contribute to diseases such as cancer, emphasizing the need for effective DNA repair pathways to mitigate these risks.
  • What role does base excision repair play in maintaining genomic integrity in relation to 8-oxoguanine?
    • Base excision repair (BER) is crucial for maintaining genomic integrity by specifically targeting and repairing damaged bases like 8-oxoguanine. In this process, specialized enzymes recognize the damaged base and initiate its removal. Following this, a new nucleotide is inserted, thus restoring the original DNA sequence and preventing the propagation of mutations that could arise from unrepaired oxidative damage.
  • Evaluate the significance of 8-oxoguanine as a biomarker for oxidative stress and its implications for health research.
    • 8-oxoguanine serves as a significant biomarker for oxidative stress, reflecting the level of oxidative damage within cells. Its measurement can provide insights into the relationship between oxidative stress and various health conditions, including cancer and neurodegenerative diseases. By understanding how oxidative stress contributes to the formation of 8-oxoguanine and subsequent mutations, researchers can develop strategies to combat these diseases through antioxidants or other therapeutic approaches aimed at reducing oxidative damage.

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