baseexcision

Base excision repair (BER) is a DNA repair pathway that corrects small base lesions resulting from oxidation, deamination, or alkylation. It is initiated by specific DNA glycosylases that recognize damaged bases and excise them, leaving an abasic (AP) site. The AP site is then processed by an AP endonuclease, which cleaves the DNA backbone at the site, producing a single-strand break with ends suitable for repair. In some cases, the glycosylase or the endonuclease also shares a sugar-phosphate removal activity to tidy the DNA end for subsequent steps.

The gap created in the DNA is filled and sealed through one of two subpathways: short-patch BER and long-patch BER. In short-patch BER, a single nucleotide is replaced and the nick is ligated. In long-patch BER, a longer patch is synthesized by a DNA polymerase, displacing the strand and creating a displaced flap that is processed before ligation. In eukaryotes, DNA polymerase beta commonly drives the short-patch route and XRCC1 serves as a scaffold; long-patch BER involves other polymerases such as delta or epsilon and associated factors. In bacteria, polymerase I and ligase mediate the repair, while mitochondria utilize a variant of BER with similar enzymatic steps.

BER targets a range of lesions, including oxidized bases such as 8-oxoguanine and misincorporated or deaminated bases like uracil. The pathway is essential for maintaining genome stability and preventing mutations. Defects in BER components can contribute to mutagenesis and have been linked to cancer susceptibility; several enzymes in BER are explored as potential targets in cancer therapy.