Base excision repair

Definition

Base excision repair is a cellular mechanism that fixes small, non-helix-distorting base lesions in DNA. This process is crucial for maintaining the integrity of genetic information by correcting various types of DNA damage, such as deaminated or oxidized bases. By recognizing and removing damaged bases, base excision repair plays an essential role in preventing mutations and ensuring the proper functioning of cellular processes.

5 Must Know Facts For Your Next Test

1. Base excision repair is initiated by DNA glycosylases, which identify and remove specific damaged bases from the DNA strand.
2. After removal of the damaged base, an AP site is formed, which is then processed by AP endonucleases that create a nick in the DNA strand.
3. Following the nick creation, DNA polymerase fills in the gap with the correct nucleotide, and DNA ligase seals the final break in the sugar-phosphate backbone.
4. This repair mechanism is particularly important for fixing oxidative damage caused by reactive oxygen species, which can arise from normal metabolic processes.
5. Failure to properly execute base excision repair can lead to mutations that contribute to various diseases, including cancer.

Review Questions

• How does base excision repair differ from other DNA repair mechanisms like nucleotide excision repair?
  • Base excision repair specifically targets small, non-helix-distorting base lesions caused by factors like oxidation or deamination, while nucleotide excision repair deals with larger, helix-distorting lesions such as thymine dimers. The processes also differ in their methods; base excision repair removes individual damaged bases through a series of steps involving DNA glycosylases and AP endonucleases, whereas nucleotide excision repair involves cutting out longer stretches of DNA around the damaged area before resynthesizing it. Understanding these differences helps clarify how cells maintain DNA integrity under various types of damage.
• Discuss the significance of DNA glycosylases in the base excision repair process.
  • DNA glycosylases are crucial enzymes that recognize and remove specific damaged bases during base excision repair. By initiating the repair process, they prevent mutations from becoming permanent fixtures in the DNA sequence. Each type of DNA glycosylase targets particular types of damage; for instance, uracil-DNA glycosylase removes uracil from DNA strands. Their function underscores the precision of the base excision repair mechanism in maintaining genomic stability.
• Evaluate how failures in base excision repair mechanisms might contribute to the development of cancer.
  • When base excision repair mechanisms fail to correct DNA damage effectively, it can lead to an accumulation of mutations within the genome. These mutations may affect key genes involved in cell cycle regulation or apoptosis, ultimately leading to uncontrolled cell growth and cancer development. Studies have shown that deficiencies in specific DNA glycosylases are linked to increased cancer risk. Thus, understanding how these failures occur provides insight into potential therapeutic targets for cancer prevention and treatment.

Related terms

DNA Glycosylases: Enzymes that initiate base excision repair by recognizing and removing damaged or incorrect bases from the DNA.

AP Site: An apurinic/apyrimidinic site created when a DNA glycosylase removes a damaged base, leaving a gap that must be repaired.

Nucleotide Excision Repair: A DNA repair mechanism that removes bulky DNA lesions and involves excising a short single-strand segment of DNA containing the damage.