Base excision repair

Definition

Base excision repair is a cellular mechanism that corrects DNA damage by removing and replacing damaged or non-canonical bases within the DNA strand. This process is vital for maintaining genomic integrity, as it addresses small-scale lesions caused by oxidative stress, alkylation, or deamination, preventing these changes from leading to mutations during DNA replication.

5 Must Know Facts For Your Next Test

1. Base excision repair primarily addresses single-base alterations, such as uracil incorporation or oxidized bases, effectively preventing mutations.
2. The process involves several key steps: recognition and removal of the damaged base by DNA glycosylase, cleavage of the DNA backbone by AP endonuclease, and subsequent gap-filling by DNA polymerase and ligation.
3. Base excision repair plays a crucial role in preventing cancer, as unrepaired DNA damage can lead to mutations that contribute to tumorigenesis.
4. This repair pathway is particularly important in post-mitotic cells, such as neurons, where maintaining genetic stability is essential for proper function.
5. Defects in base excision repair mechanisms have been linked to various genetic disorders and increased susceptibility to certain types of cancers.

Review Questions

• How does base excision repair specifically target small-scale DNA damage, and what are the main enzymes involved in this process?
  • Base excision repair specifically targets small-scale DNA damage, such as single-base alterations and non-canonical bases. The main enzymes involved include DNA glycosylases that recognize and remove damaged bases, followed by AP endonuclease that cleaves the DNA backbone at the abasic site. These coordinated actions ensure efficient repair of the DNA strand and help maintain genomic stability.
• Compare base excision repair with nucleotide excision repair in terms of the types of DNA damage they address and their mechanisms.
  • Base excision repair focuses on small-scale modifications, like damaged or incorrect bases, while nucleotide excision repair deals with bulky lesions like thymine dimers caused by UV radiation. In base excision repair, damaged bases are removed by glycosylases, followed by cleavage and synthesis steps. In contrast, nucleotide excision repair involves a more extensive incision process around the lesion before removal and replacement of the entire damaged segment.
• Evaluate the implications of defective base excision repair mechanisms on cellular health and cancer risk.
  • Defective base excision repair mechanisms can have severe implications for cellular health by allowing the accumulation of DNA damage over time. This accumulation increases the likelihood of mutations during cell division, which can lead to tumorigenesis and various genetic disorders. Therefore, understanding and targeting these pathways in cancer therapies is critical for developing effective treatments that restore normal DNA repair functions.

Related terms

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

AP endonuclease: An enzyme that cleaves the DNA backbone at abasic sites, creating a nick that facilitates further repair steps in base excision repair.

Nucleotide excision repair: A DNA repair mechanism that removes bulky DNA lesions, unlike base excision repair, which focuses on smaller base modifications.