8-oxoguanine

Definition

8-oxoguanine is a modified form of the nucleotide guanine that occurs when DNA is exposed to oxidative stress, often resulting from reactive oxygen species. This alteration can lead to mispairing during DNA replication, causing mutations and potentially contributing to various diseases, including cancer. The presence of 8-oxoguanine highlights the importance of DNA repair mechanisms that can recognize and correct such modifications to maintain genomic integrity.

5 Must Know Facts For Your Next Test

1. 8-oxoguanine is formed when guanine in DNA undergoes oxidation, making it a common marker of oxidative damage.
2. This modified nucleotide can pair with adenine instead of cytosine during DNA replication, leading to G:C to T:A transversions.
3. The accumulation of 8-oxoguanine in cells is associated with aging and age-related diseases due to increased oxidative stress over time.
4. Cells have evolved repair pathways, like base excision repair, specifically targeting 8-oxoguanine to prevent mutations from becoming permanent.
5. Measuring levels of 8-oxoguanine in biological samples can serve as a biomarker for oxidative stress and the potential risk of certain diseases.

Review Questions

• How does 8-oxoguanine formation impact the accuracy of DNA replication?
  • The formation of 8-oxoguanine affects DNA replication by introducing the possibility of mispairing with adenine instead of the normal pairing with cytosine. This mispairing can lead to mutations, specifically G:C to T:A transversions, which can accumulate over time if not corrected. Such mutations can disrupt gene function and contribute to diseases like cancer, emphasizing the need for effective DNA repair mechanisms.
• Discuss the role of base excision repair in correcting damage caused by 8-oxoguanine and its significance in maintaining genomic stability.
  • Base excision repair plays a crucial role in correcting the damage caused by 8-oxoguanine. This repair pathway recognizes the altered nucleotide and removes it, allowing DNA polymerase to insert the correct base in its place. By effectively repairing this oxidative damage, base excision repair helps maintain genomic stability and prevents the propagation of mutations that could lead to cellular dysfunction and disease.
• Evaluate the relationship between oxidative stress, 8-oxoguanine levels, and the onset of age-related diseases.
  • There is a significant relationship between oxidative stress and elevated levels of 8-oxoguanine, as oxidative stress leads to increased production of reactive oxygen species that damage DNA. As organisms age, the accumulation of 8-oxoguanine becomes more pronounced due to the decline in effective repair mechanisms. This accumulation can contribute to the development of age-related diseases, including cancer and neurodegenerative disorders, highlighting the importance of managing oxidative stress to promote healthier aging.

Related terms

Oxidative Stress: A condition characterized by excessive reactive oxygen species (ROS) that can damage cellular components, including DNA, proteins, and lipids.

Base Excision Repair: A cellular mechanism that repairs damaged DNA by removing and replacing non-canonical bases, such as 8-oxoguanine.

Reactive Oxygen Species: Highly reactive molecules derived from oxygen that can cause significant damage to cellular structures, including DNA.