Biochemistry

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8-oxoguanine

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Biochemistry

Definition

8-oxoguanine is a modified nucleobase formed by the oxidation of guanine, which can mispair with adenine during DNA replication, leading to G:C to T:A transversions. This abnormal base is a common marker of oxidative DNA damage and plays a crucial role in DNA repair mechanisms that maintain genomic stability.

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5 Must Know Facts For Your Next Test

  1. 8-oxoguanine is considered one of the most prevalent forms of oxidative damage to DNA and is linked to various diseases, including cancer.
  2. The presence of 8-oxoguanine in DNA can lead to replication errors if not repaired, increasing the risk of mutations.
  3. Cells have evolved specific repair pathways, such as the base excision repair pathway, to correct 8-oxoguanine and prevent its propagation during cell division.
  4. Detection of 8-oxoguanine can be used as a biomarker for oxidative stress and DNA damage in biological samples.
  5. The formation of 8-oxoguanine is often induced by environmental factors like UV radiation and pollution, highlighting the impact of external stressors on DNA integrity.

Review Questions

  • How does 8-oxoguanine contribute to mutagenesis during DNA replication?
    • 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, as the incorrect base pairing can be retained in subsequent rounds of replication. Understanding this mechanism is essential for comprehending how oxidative damage impacts genetic stability and contributes to the development of diseases like cancer.
  • Evaluate the importance of base excision repair in addressing the damage caused by 8-oxoguanine.
    • Base excision repair is crucial for maintaining genomic integrity by repairing damaged bases like 8-oxoguanine. This pathway involves recognition and removal of the damaged base by specific glycosylases, followed by gap filling and ligation processes. Effective base excision repair prevents the accumulation of mutations and ensures proper cellular function, highlighting its role in protecting cells from the harmful effects of oxidative stress.
  • Analyze the implications of elevated levels of 8-oxoguanine in cells and their relationship to disease states.
    • Elevated levels of 8-oxoguanine indicate increased oxidative stress and potential dysfunction in DNA repair mechanisms. Such accumulations can lead to higher mutation rates, contributing to tumorigenesis and other disease states. The correlation between oxidative damage marked by 8-oxoguanine and diseases like cancer emphasizes the importance of understanding this biomarker for early detection and intervention strategies in clinical settings.

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