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- W1971997637 abstract "Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is the redox regulator of multiple stress-inducible transcription factors, such as NF-κB, and the major 5′-endonuclease in base excision repair (BER). We utilized mice containing a heterozygous gene-targeted deletion of APE1/Ref-1 (Apex+/−) to determine the impact of APE1/Ref-1 haploinsufficiency on the processing of oxidative DNA damage induced by 2-nitropropane (2-NP) in the liver tissue of mice. APE1/Ref-1 haploinsufficiency results in a significant decline in NF-κB DNA-binding activity in response to oxidative stress in liver. In addition, loss of APE1/Ref-1 increases the apoptotic response to oxidative stress, in which significant increases in GADD45g expression, p53 protein stability, and caspase activity are observed. Oxidative stress displays a differential impact on monofunctional (UNG) and bifunctional (OGG1) DNA glycosylase-initiated BER in the liver of Apex+/− mice. APE1/Ref-1 haploinsufficiency results in a significant decline in the repair of oxidized bases (e.g., 8-OHdG), whereas removal of uracil is increased in liver nuclear extracts of mice using an in vitro BER assay. Apex+/− mice exposed to 2-NP displayed a significant decline in 3′-OH-containing single-strand breaks and an increase in aldehydic lesions in their liver DNA, suggesting an accumulation of repair intermediates of failed bifunctional DNA glycosylase-initiated BER." @default.
- W1971997637 created "2016-06-24" @default.
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- W1971997637 date "2009-06-01" @default.
- W1971997637 modified "2023-10-16" @default.
- W1971997637 title "Oxidative stress alters base excision repair pathway and increases apoptotic response in apurinic/apyrimidinic endonuclease 1/redox factor-1 haploinsufficient mice" @default.
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- W1971997637 doi "https://doi.org/10.1016/j.freeradbiomed.2009.02.021" @default.
- W1971997637 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2677124" @default.
- W1971997637 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19268524" @default.
- W1971997637 hasPublicationYear "2009" @default.
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