FIGURE 6:

Mechanistic model for the role of APE1 in oxidatively mediated SIRT1 transcription. Under normal conditions, APE1, together with other protein factors, is bound to the nCaRE element present within the SIRT1 promoter involved in the basal activation of SIRT1 transcription. Conversely, upon oxidative stress conditions, DNA oxidation determines the formation of 8-oxodeoxyguanine (8-oxoG) lesions at the nCaRE sequence present in the SIRT1 promoter, which are recognized and processed by BER enzymes, including APE1. The nicks introduced at the chromatin level by APE1 during 8-oxoG removal might promote the formation of chromatin loops moving the active form of RNA polymerase II closer to the TSS of the gene, turning on the transcription.