Base excision repair

Definition

Base excision repair is a cellular mechanism that corrects DNA damage, specifically small, non-helix-distorting base lesions. This process plays a crucial role in maintaining genome integrity by removing and replacing damaged bases, which can arise from factors like oxidative stress or deamination. By recognizing and fixing these lesions, base excision repair helps prevent mutations that could lead to diseases like cancer.

5 Must Know Facts For Your Next Test

1. Base excision repair is initiated by DNA glycosylases, which identify and remove the damaged base, leaving an abasic site.
2. After the removal of the damaged base, an endonuclease cleaves the DNA backbone at the abasic site, preparing for further repair.
3. DNA polymerase then synthesizes a new nucleotide to fill in the gap left by the missing base, followed by DNA ligase sealing the nick in the sugar-phosphate backbone.
4. This repair pathway is essential for fixing common forms of DNA damage like oxidized bases, which can occur due to environmental stressors or normal metabolic processes.
5. Deficiencies in base excision repair mechanisms have been linked to various genetic disorders and increased susceptibility to cancer due to the accumulation of mutations.

Review Questions

• How does base excision repair differ from other DNA repair mechanisms?
  • Base excision repair is specifically designed to fix small, non-helix-distorting lesions in DNA, such as damaged bases caused by oxidation or deamination. Unlike nucleotide excision repair, which removes larger segments of DNA containing bulky adducts, base excision repair focuses on individual base corrections. The precision of this mechanism helps maintain genetic stability by effectively preventing mutations that could arise from unrepaired lesions.
• Discuss the role of DNA glycosylases in base excision repair and how they contribute to overall genomic integrity.
  • DNA glycosylases are crucial initiators in the base excision repair process as they identify and remove specific damaged bases from the DNA strand. By cleaving the N-glycosidic bond at the site of damage, they create an abasic site that signals further steps for repair. This action prevents potentially harmful mutations from accumulating, thereby maintaining genomic integrity and protecting against diseases like cancer that can arise from DNA damage.
• Evaluate the implications of impaired base excision repair on human health and disease susceptibility.
  • Impaired base excision repair mechanisms can lead to an accumulation of unrepaired DNA damage, resulting in increased mutation rates and a higher risk of developing various diseases, including cancer. For instance, individuals with inherited deficiencies in certain DNA glycosylases may show a predisposition to specific cancers due to their cells' inability to effectively correct minor but significant genetic errors. This highlights the importance of a functional base excision repair pathway in preventing genomic instability and maintaining overall health.

Related terms

DNA glycosylase: An enzyme that recognizes and removes damaged bases during base excision repair by cleaving the N-glycosidic bond.

Single-strand break repair: A repair process that fixes breaks in one strand of the DNA helix, often involving mechanisms similar to those of base excision repair.

Nucleotide excision repair: A DNA repair pathway that removes bulky DNA adducts and replaces them with newly synthesized DNA, differing from the more precise base excision repair.