Base excision repair

Definition

Base excision repair (BER) is a cellular mechanism that corrects DNA damage by removing and replacing damaged or non-canonical bases. This process is crucial for maintaining the integrity of the genetic material by fixing small lesions that could lead to mutations if left unrepaired. The efficiency of BER plays a significant role in preventing mutations, thus helping to protect the organism from various diseases, including cancer.

5 Must Know Facts For Your Next Test

1. Base excision repair primarily targets small base lesions, such as those caused by oxidation, alkylation, or deamination.
2. The process involves several key steps: recognition of the damaged base, removal of the base by DNA glycosylases, and subsequent cleavage of the DNA backbone by an AP endonuclease.
3. Following the creation of an AP site, DNA polymerase synthesizes a new nucleotide to replace the removed base, and DNA ligase seals the remaining gap.
4. BER is essential for cellular health, as errors in this repair process can lead to mutations that contribute to diseases like cancer.
5. In humans, defects in base excision repair mechanisms have been linked to several genetic disorders and increased cancer susceptibility.

Review Questions

• How does base excision repair specifically target and fix damaged bases in DNA?
  • Base excision repair targets damaged bases by using specific enzymes called DNA glycosylases that recognize and remove abnormal bases. Once a damaged base is identified, it is excised, creating an AP site. This site is then processed by an AP endonuclease that cleaves the DNA backbone, allowing for a new nucleotide to be inserted by DNA polymerase before finally sealing the gap with DNA ligase.
• Discuss the differences between base excision repair and nucleotide excision repair in terms of their mechanisms and types of damage they address.
  • Base excision repair is designed to correct small, non-helix-distorting base lesions caused by factors like oxidation or deamination. In contrast, nucleotide excision repair is geared towards removing bulky DNA adducts and helix-distorting lesions such as those caused by UV light. While both mechanisms involve recognition of damage and restoration of DNA integrity, their specific processes and types of damage targeted are distinct.
• Evaluate the implications of defective base excision repair on human health and its potential link to cancer development.
  • Defective base excision repair can lead to an accumulation of mutations in the genome due to the inability to effectively correct minor DNA lesions. This accumulation can disrupt critical genes involved in cell cycle regulation and apoptosis, paving the way for oncogenic transformations. The link between impaired BER pathways and increased cancer susceptibility highlights the importance of these repair mechanisms in maintaining genomic stability and overall health.

Related terms

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

AP site: A site in DNA that has lost a purine or pyrimidine base, which is an intermediate during base excision repair.

Nucleotide excision repair: A DNA repair mechanism that removes bulky DNA lesions, contrasting with the more targeted approach of base excision repair.