Base excision repair pathway

Definition

The base excision repair pathway is a cellular mechanism that repairs damaged DNA by removing and replacing individual bases, ensuring the integrity of the genetic material. This process is crucial for fixing small, non-helix-distorting lesions such as oxidative damage or deamination, which can lead to mutations if not corrected. By maintaining DNA stability, this pathway plays a vital role in cellular health and can be influenced by various epigenetic factors.

5 Must Know Facts For Your Next Test

1. Base excision repair is initiated when DNA glycosylases identify and remove damaged bases, creating an abasic site in the DNA.
2. Following the removal of a damaged base, AP endonucleases cleave the DNA backbone, allowing other enzymes to fill in the gap with the correct nucleotide.
3. This pathway is particularly important for repairing lesions caused by environmental factors such as UV radiation or chemical exposure.
4. Epigenetic modifications like DNA methylation can impact the efficiency of base excision repair, potentially altering how effectively cells respond to DNA damage.
5. Defects in the base excision repair pathway are associated with various diseases, including cancer, highlighting its importance in maintaining genomic stability.

Review Questions

• How does the base excision repair pathway work to fix damaged DNA?
  • The base excision repair pathway begins when DNA glycosylases detect and remove damaged bases, creating an abasic site. Next, AP endonucleases introduce a break in the DNA backbone at this site. Following this, DNA polymerases fill in the gap with the correct nucleotide, and finally, DNA ligases seal the strand to restore the integrity of the DNA. This multi-step process is essential for correcting small lesions that can lead to mutations.
• Discuss how DNA methylation might influence the base excision repair pathway.
  • DNA methylation can influence gene expression and subsequently affect proteins involved in the base excision repair pathway. Increased methylation of promoter regions may silence genes encoding key repair enzymes, leading to reduced efficiency in repairing damaged DNA. This can result in an accumulation of mutations and genomic instability, which is particularly concerning in cells that are rapidly dividing or under stress from environmental damage.
• Evaluate the implications of impaired base excision repair on human health and disease.
  • Impaired base excision repair can lead to an accumulation of DNA damage, increasing the risk of mutations that contribute to various diseases, including cancer. When this repair mechanism fails, cells may proliferate with unrepaired genetic alterations, ultimately leading to tumorigenesis. Additionally, individuals with genetic defects in components of this pathway may exhibit increased sensitivity to certain environmental toxins or radiations that cause DNA damage, further complicating their health outcomes.

Related terms

DNA glycosylases: Enzymes that recognize and remove damaged bases from DNA during the base excision repair process.

AP endonuclease: An enzyme that creates a break in the DNA backbone at an apurinic or apyrimidinic site, facilitating further repair steps in the base excision repair pathway.

Methylation: A common epigenetic modification where methyl groups are added to DNA, influencing gene expression and potentially affecting DNA repair mechanisms.