Base excision repair

Definition

Base excision repair is a cellular mechanism that corrects DNA damage caused by the removal of damaged or non-canonical bases. This process is essential for maintaining genomic stability by fixing small, non-helix-distorting base lesions that may result from environmental factors or normal cellular metabolism. By efficiently identifying and excising damaged bases, base excision repair prevents mutations that could lead to diseases, including cancer.

5 Must Know Facts For Your Next Test

1. Base excision repair primarily addresses damage caused by oxidation, alkylation, and deamination of DNA 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 an AP site is formed, an AP endonuclease enzyme cuts the DNA strand at the site, allowing for subsequent repair synthesis.
4. DNA polymerase then fills in the gap with the correct nucleotide, followed by DNA ligase sealing the remaining nick to restore the DNA strand.
5. Base excision repair is crucial in preventing mutations and maintaining the integrity of the genome, particularly in regions of active transcription.

Review Questions

• How does the base excision repair mechanism recognize and remove damaged bases in DNA?
  • Base excision repair recognizes damaged bases through specific enzymes known as DNA glycosylases. These enzymes scan the DNA for non-canonical bases or those modified by damage. Upon identification, they cleave the bond between the damaged base and the sugar backbone, creating an apurinic/apyrimidinic (AP) site, which is further processed by other enzymes to complete the repair.
• Compare and contrast base excision repair with nucleotide excision repair in terms of their mechanisms and types of damage they address.
  • Base excision repair specifically targets small, non-helix-distorting lesions caused by oxidative stress or alkylation, utilizing DNA glycosylases to remove damaged bases one at a time. In contrast, nucleotide excision repair deals with bulky adducts or helix-distorting lesions by removing a short segment of the damaged strand. This difference reflects their respective roles in maintaining genomic stability under various types of DNA damage.
• Evaluate the significance of base excision repair in cancer prevention and how its dysfunction can contribute to tumorigenesis.
  • Base excision repair plays a crucial role in preventing mutations that can lead to cancer. By efficiently repairing small base damages, it helps maintain genomic integrity. Dysfunction in this repair pathway can result in the accumulation of mutations, leading to genomic instability and increased susceptibility to tumorigenesis. Studies have shown that defects in key components of base excision repair are associated with certain cancers, highlighting its importance in maintaining cellular health.

Related terms

DNA glycosylase: An enzyme that recognizes and removes damaged or mispaired bases in DNA during the base excision repair process.

AP site: A location in DNA that has lost a purine or pyrimidine base, often resulting from the action of DNA glycosylases in the base excision repair pathway.

nucleotide excision repair:

A DNA repair mechanism that removes bulky DNA lesions and larger sections of damaged DNA, differing from base excision repair, which targets single base alterations.