Copyright information:Taken from "Oxidative stress-induced apoptosis in neurons correlates with mitochondrial DNA base excision repair pathway imbalance"Nucleic Acids Research 2005;33(14):4660-4671.Published online 17 Aug 2005PMCID:PMC1187820.©The Author 2005. Published by Oxford University Press. All rights reserved In addition to oxidized bases, oxidative DNA damage may also include damage to the deoxyribose sugar backbone, which can result in the direct release of bases forming AP sites. The bifunctional glycosylase/AP lyases (AP lyase) excise oxidatively damaged bases, such as 8-oxoguanine, prior to incising the sugar backbone 3′ to the lesion. AP sites are substrates for either AP endonuclease (APE/Ref-1) or the AP lyases and are processed by these two pathway initiators producing single strand breaks: 3′-OH/5′-deoxyribose phosphate (5′-dRP) and 5′-phosphate/3′-fragmented deoxyribose, respectively. The 5′-dRP product of APE/Ref-1 is removed by the dRPase activity of pol γ, and the 3′-fragmented deoxyribose product of the AP lyase is removed by the 3′-diesterase activity of APE/Ref-1. Once the single nucleotide gap has been processed, pol γ can fill the gap. The remaining DNA strand break is sealed by DNA ligase. Pathway arrows are drawn in boldface to indicate the relative high AP lyase and APE activities and low pol γ activity measured in cerebellar granule cell mitochondria. Imbalanced BER can result in accumulation of cytotoxic pathway intermediates.