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Base excision repair (BER) is a DNA repair pathway that removes damaged or incorrect bases from DNA and replaces them with correct nucleotides. This process is critical for maintaining genomic stability and preventing mutations that could lead to cell dysfunction or disease. BER protects cells from the accumulation of DNA damage caused by oxidative stress and other cellular processes.

Base excision repair targets small lesions affecting individual bases, while nucleotide excision repair removes larger DNA segments containing multiple damaged nucleotides. BER uses specific glycosylases to recognize and remove damaged bases, whereas nucleotide excision repair involves removal of an oligonucleotide segment. Both pathways are essential for different types of DNA damage recognition and repair.

Base excision repair begins with damage recognition by DNA glycosylases, which remove the damaged base and create an abasic site. AP endonuclease then cleaves the DNA backbone at the abasic site. DNA polymerase fills the gap with the correct nucleotide, and DNA ligase seals the nick to complete repair. This coordinated enzyme action restores DNA integrity.

DNA glycosylases are the primary enzymes that recognize and remove damaged bases during base excision repair. Different glycosylases recognize specific types of base damage, such as oxidized bases or uracil residues. These enzymes catalyze hydrolysis of the N-glycosidic bond connecting the damaged base to the sugar-phosphate backbone, initiating the repair cascade.

Base excision repair primarily addresses small, single-base lesions including oxidized bases, deaminated bases, and alkylated bases. These lesions result from oxidative stress, spontaneous deamination, and chemical exposure. BER is particularly important for repairing damage from reactive oxygen species, making it essential for protecting cells from metabolic byproducts and environmental stressors.

Base excision repair maintains genomic stability by promptly removing damaged bases before they can cause mutations during DNA replication. By restoring correct base pairing and its significance in DNA replication, BER prevents the propagation of errors to daughter cells. Defects in BER pathways are associated with increased mutation rates and cancer susceptibility.

Defective base excision repair leads to accumulation of unrepaired DNA lesions, increasing mutation rates and genomic instability. This can result in cell cycle arrest, apoptosis, or uncontrolled cell proliferation. Impaired BER is linked to cancer development, neurological disorders, and premature aging, highlighting the critical role of this repair pathway in cellular health.