Base excision repair

Definition

Base excision repair is a critical DNA repair mechanism that corrects small, non-helix-distorting base lesions in the DNA molecule. This process involves recognizing and removing damaged or incorrect bases, followed by synthesizing the correct nucleotide to restore the DNA's integrity. Base excision repair is essential for maintaining genetic stability and preventing mutations that could lead to diseases such as cancer.

5 Must Know Facts For Your Next Test

1. Base excision repair is primarily responsible for correcting damage caused by oxidative stress, deamination, and alkylation of bases.
2. The process begins with a DNA glycosylase recognizing the damaged base and cleaving the N-glycosidic bond to create an AP site.
3. After the removal of the damaged base, an AP endonuclease cuts the DNA backbone at the AP site, allowing for subsequent steps in repair.
4. DNA polymerase then fills in the gap with the correct nucleotide before DNA ligase seals the final nick in the DNA strand.
5. This repair pathway is crucial for preventing mutations that can arise from unrepaired base damage and is active throughout the cell cycle.

Review Questions

• How does base excision repair differ from nucleotide excision repair in terms of their mechanisms and the types of damage they address?
  • Base excision repair specifically targets small, non-helix-distorting base lesions caused by factors like oxidative damage or deamination. In contrast, nucleotide excision repair addresses larger, bulky DNA adducts that distort the helical structure of DNA. While both processes are vital for maintaining genomic integrity, they involve different enzymes and mechanisms to recognize and repair distinct types of DNA damage.
• Discuss the role of DNA glycosylases in base excision repair and how they initiate the repair process.
  • DNA glycosylases play a crucial role in base excision repair by recognizing and removing damaged bases from the DNA strand. Once a glycosylase identifies a damaged or incorrect base, it cleaves the N-glycosidic bond, resulting in an AP site. This action initiates a cascade of repair events, including AP endonuclease activity and subsequent filling of the gap by DNA polymerase, ensuring that the integrity of the DNA is restored.
• Evaluate the significance of base excision repair in preventing genetic diseases and its potential implications in cancer research.
  • Base excision repair is significant in preventing genetic diseases as it corrects common forms of DNA damage that can lead to mutations if left unrepaired. A failure in this pathway can result in increased mutagenesis and contribute to the development of cancers. Understanding this mechanism is essential for cancer research since targeting specific components of base excision repair could enhance cancer therapies by making tumor cells more susceptible to damage or improving normal tissue recovery after treatment.

Related terms

DNA glycosylase: An enzyme that recognizes and removes damaged or non-canonical bases from DNA, initiating the base excision repair process.

AP site: A site in DNA that has lost a base, creating an apurinic or apyrimidinic (AP) site, which must be repaired to maintain DNA integrity.

Nucleotide excision repair: A DNA repair mechanism that removes bulky, helix-distorting lesions, unlike base excision repair, which targets smaller base changes.