- DNA Polymerase β (Pol β) is a DNA-dependent DNA polymerase primarily involved in base excision repair (BER) in eukaryotic cells. It plays a crucial role in maintaining genomic integrity by repairing small base lesions that arise due to oxidation, alkylation, or deamination. Unlike replicative DNA polymerases, Pol β is a monomeric, low-processivity enzyme specialized for short-patch repair rather than long DNA synthesis.
- Structurally, DNA polymerase β consists of two main domains: a polymerase domain, which catalyzes the addition of deoxyribonucleotides to the 3′ end of a DNA strand, and an 8-kDa lyase domain, which removes the 5′ deoxyribose phosphate (dRP) moiety left behind after damaged bases are excised by glycosylases and endonucleases. This dual functionality enables Pol β to fill in single-nucleotide gaps and clean up abasic sites efficiently.
- Functionally, Pol β operates in the base excision repair pathway, which is initiated when a DNA glycosylase recognizes and removes a damaged base, leaving behind an abasic site. AP endonuclease then cleaves the phosphodiester backbone 5′ to the site, generating a single-nucleotide gap. At this point, Pol β inserts the correct nucleotide and removes the 5′ sugar phosphate, allowing DNA ligase to seal the nick.
- Although Pol β lacks 3′→5′ exonuclease proofreading activity, its fidelity is considered acceptable given its limited role in short, targeted repair synthesis. However, Pol β is one of the most commonly mutated DNA polymerases in human tumors, and such mutations can lead to genomic instability or mutagenic repair.
- In conclusion, DNA polymerase β is a specialized repair polymerase critical for fixing endogenous DNA damage via the base excision repair pathway. Its dual polymerase and lyase functions make it essential for maintaining genome stability, and its dysfunction is closely associated with cancer and aging.
