Ap endonuclease

Definition

Ap endonuclease is an enzyme that plays a crucial role in DNA repair by recognizing and removing damaged or missing nucleotides, specifically at apurinic/apyrimidinic (AP) sites in the DNA strand. This enzyme is essential for the base excision repair (BER) pathway, helping to maintain the integrity of genetic material by repairing non-helix-distorting lesions that can arise from spontaneous hydrolysis or chemical damage.

5 Must Know Facts For Your Next Test

1. Ap endonucleases create a nick in the DNA backbone at the AP site, allowing for subsequent repair steps to take place.
2. They are classified as either class I or class II based on their structural and functional properties, with class I enzymes requiring magnesium ions for activity.
3. In humans, the main ap endonuclease involved in DNA repair is APEX1, which also has roles in regulating gene expression and apoptosis.
4. The activity of ap endonuclease is critical for preventing mutations that could lead to diseases such as cancer due to accumulated DNA damage.
5. Deficiencies in ap endonuclease function can result in increased sensitivity to DNA-damaging agents, highlighting its importance in maintaining genomic stability.

Review Questions

• How does ap endonuclease function within the base excision repair pathway, and why is this process vital for cellular health?
  • Ap endonuclease functions within the base excision repair pathway by recognizing AP sites that result from the removal of damaged bases. Once it identifies these sites, it cleaves the DNA backbone at the AP site, facilitating further repair by allowing DNA polymerase to fill in the gap with correct nucleotides. This process is vital for cellular health because it helps prevent mutations and maintains the integrity of the genetic material, reducing the risk of diseases such as cancer.
• Discuss the role of DNA glycosylases in relation to ap endonuclease and how they contribute to the overall DNA repair mechanism.
  • DNA glycosylases are crucial for initiating the base excision repair process by locating and removing damaged bases from the DNA strand. Once a glycosylase removes a base, it creates an AP site that is then targeted by ap endonuclease. The coordination between these two enzymes ensures that damaged bases are efficiently repaired, highlighting their interdependence in maintaining genomic stability and preventing potential mutations that could lead to cellular dysfunction.
• Evaluate the implications of defective ap endonuclease activity on human health, particularly concerning cancer development and treatment outcomes.
  • Defective ap endonuclease activity can have serious implications for human health by leading to an accumulation of DNA damage due to ineffective repair mechanisms. This accumulation increases the likelihood of mutations, which can initiate carcinogenesis and contribute to cancer development. Additionally, individuals with impaired ap endonuclease function may exhibit increased sensitivity to DNA-damaging agents used in cancer therapies, potentially complicating treatment outcomes. Understanding these connections emphasizes the importance of efficient DNA repair processes in preventing disease.

Related terms

Base Excision Repair (BER): A DNA repair pathway that removes and replaces damaged or non-canonical bases in the DNA, involving several enzymes including DNA glycosylases and ap endonuclease.

DNA Glycosylase: An enzyme responsible for identifying and removing specific damaged bases from DNA, creating an AP site that is then processed by ap endonuclease.

Nucleotide Excision Repair (NER): A DNA repair mechanism that removes bulky DNA adducts and other helix-distorting lesions, which is different from the function of ap endonuclease in BER.