Base Excision Repair

Definition

Base excision repair (BER) is a crucial DNA repair mechanism that removes and replaces damaged or non-canonical bases in DNA. This process is vital for maintaining genomic integrity, as it specifically targets small-scale lesions like oxidized, alkylated, or deaminated bases, which can lead to mutations if left unrepaired. BER works through a series of coordinated steps involving DNA glycosylases, which recognize and excise the faulty base, followed by the recruitment of other enzymes to fill in the gap and restore the correct DNA sequence.

5 Must Know Facts For Your Next Test

1. Base excision repair primarily corrects non-helix-distorting base damage, making it essential for fixing oxidative DNA damage caused by reactive oxygen species.
2. The BER pathway begins with the recognition of the damaged base by a specific DNA glycosylase, which cleaves the N-glycosidic bond to release the altered base.
3. After base removal, an apurinic/apyrimidinic (AP) site is created, which is then processed by an AP endonuclease that cuts the DNA backbone at this location.
4. DNA polymerase then fills the gap by synthesizing new nucleotides to replace the missing base, followed by DNA ligase sealing the final nick in the backbone.
5. Defects in base excision repair can lead to genetic disorders and contribute to cancer development due to accumulated mutations.

Review Questions

• How does base excision repair initiate the process of correcting damaged DNA bases?
  • Base excision repair starts with a specialized enzyme called a DNA glycosylase that identifies and binds to damaged or inappropriate bases in the DNA. Once recognized, the glycosylase cleaves the bond between the damaged base and the sugar-phosphate backbone, releasing the faulty base. This initial step creates an apurinic/apyrimidinic site, setting off a cascade of reactions involving additional enzymes to complete the repair.
• Compare and contrast base excision repair with nucleotide excision repair regarding their mechanisms and types of damage they address.
  • Base excision repair focuses on repairing small, non-bulky DNA lesions like oxidized or deaminated bases through a specific sequence of steps involving glycosylases. In contrast, nucleotide excision repair deals with bulky adducts that distort the DNA helix structure. While both processes are essential for maintaining genomic stability, they differ significantly in their substrate specificity and mechanisms of action; BER is more precise for small-scale damage while NER handles larger-scale alterations.
• Evaluate the implications of impaired base excision repair on cellular function and disease development.
  • Impaired base excision repair can have serious consequences for cellular function as it leads to an accumulation of mutations due to unresolved DNA damage. This malfunction can disrupt normal cellular processes such as replication and transcription, potentially resulting in cell death or uncontrolled proliferation. Moreover, it has been linked to various genetic disorders and plays a significant role in tumorigenesis, where persistent mutations contribute to cancer development. Understanding these implications helps in researching targeted therapies for conditions arising from defective DNA repair mechanisms.

Related terms

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

Single-Strand Break Repair: A DNA repair pathway that fixes breaks in one of the two strands of the DNA double helix, often working alongside base excision repair mechanisms.

Nucleotide Excision Repair: A DNA repair mechanism that removes bulky lesions from DNA, which is different from the more specific base excision repair process.