AP endonuclease

Definition

AP endonuclease is an enzyme that plays a crucial role in the base excision repair pathway by recognizing and cleaving apurinic/apyrimidinic (AP) sites in DNA. These AP sites occur when a nitrogenous base is lost, leaving a gap in the DNA strand that can lead to mutations if not repaired. This enzyme facilitates the removal of damaged DNA, allowing for proper repair mechanisms to restore the integrity of the genetic material.

5 Must Know Facts For Your Next Test

1. AP endonuclease specifically recognizes AP sites generated by the loss of bases due to hydrolysis or oxidative damage.
2. The activity of AP endonuclease is essential for preventing mutations that can arise from unrepaired AP sites in the DNA.
3. This enzyme functions by introducing a single-strand break at the AP site, which then allows other repair enzymes to access and correct the damaged region.
4. In humans, the primary AP endonuclease is known as APE1 (Apurinic/Apyrimidinic Endonuclease 1), which also has roles beyond DNA repair, including regulation of gene expression.
5. Deficiencies or mutations in AP endonuclease can lead to increased susceptibility to cancer and other genetic disorders due to compromised DNA repair mechanisms.

Review Questions

• How does AP endonuclease contribute to maintaining genetic stability within the cell?
  • AP endonuclease contributes to genetic stability by repairing apurinic/apyrimidinic sites in DNA, which can occur due to spontaneous hydrolysis or damage from environmental factors. By recognizing these sites and cleaving them, AP endonuclease prevents potential mutations during DNA replication. This enzymatic action ensures that the integrity of the genetic material is preserved, reducing the likelihood of errors that could lead to diseases like cancer.
• Discuss the relationship between AP endonuclease and base excision repair mechanisms.
  • AP endonuclease is a key player in the base excision repair (BER) pathway, which is responsible for fixing small-scale DNA damage caused by various factors. When a nitrogenous base is lost, it creates an AP site that needs repair. AP endonuclease recognizes this site, cleaves the sugar-phosphate backbone at the location, and creates a single-strand break. This action initiates the BER process by allowing other enzymes, such as DNA polymerase and ligase, to fill in and seal the gap, effectively restoring the DNA strand.
• Evaluate the implications of deficiencies in AP endonuclease activity on human health and disease.
  • Deficiencies in AP endonuclease activity can have serious implications for human health, particularly in increasing the risk of cancer and other genetic disorders. Without proper functioning of this enzyme, damaged DNA containing apurinic/apyrimidinic sites may go unrepaired, leading to mutations during replication. The accumulation of such mutations can disrupt normal cellular functions and contribute to tumorigenesis. Additionally, impaired DNA repair mechanisms can affect overall genomic stability, making cells more susceptible to further genetic damage and diseases associated with genomic instability.

Related terms

Base Excision Repair: A cellular mechanism that repairs damaged DNA by removing and replacing individual nucleotides to maintain genetic stability.

Apurinic Site: A site in DNA that has lost a purine base, resulting in a gap that can cause disruptions in DNA replication and transcription.

DNA Polymerase: An enzyme responsible for synthesizing new DNA strands by adding nucleotides to an existing strand during DNA replication and repair.