Base excision repair pathway components (BER pathway)

The Base Excision Repair (BER) pathway is a critical DNA repair mechanism responsible for identifying and fixing small, non-bulky lesions such as oxidized, alkylated, or deaminated bases. The process is initiated by DNA glycosylases that recognize specific damaged bases, followed by the action of AP endonuclease (APE1), DNA polymerases (primarily Pol beta), and DNA ligases (LIG1 or LIG3/XRCC1) to restore the DNA sequence (Krokan & Bjoras, 2013, PMID: 23583672). BER is essential for maintaining genomic integrity against endogenous damage caused by reactive oxygen species and metabolic byproducts (Wallace, 2014, PMID: 24441114). In oncology, components of the BER pathway, most notably PARP1, are targeted to induce synthetic lethality in tumors with pre-existing defects in other repair pathways, such as homologous recombination (Lord & Ashworth, 2017, PMID: 28115444). Beyond PARP, inhibitors of APE1 and DNA polymerase beta are being investigated to sensitize cancer cells to DNA-damaging chemotherapy and radiation (Abbotts & Madhusudan, 2010, PMID: 20510231). Dysregulation of BER components is also linked to neurodegenerative conditions and aging-related pathologies (Jeppesen et al., 2011, PMID: 21385871).

Other names

BER pathwayDNA base excision repairShort-patch repairLong-patch repair

Inhibition of specific enzymes within the pathway (e.g., PARP1, APE1, or Pol beta) to prevent the repair of DNA single-strand breaks and base lesions, leading to the accumulation of toxic DNA intermediates, replication fork collapse, and synthetic lethality in repair-deficient cells.