Skip to main content
. 2020 Aug 19;10:1575. doi: 10.3389/fonc.2020.01575

FIGURE 2.

FIGURE 2

Methoxyamine permanently modifies AP sites and prevents their repair by BER. Reactive oxygen species (ROS) modify guanine bases in DNA, which are recognized and cut by type II DNA glycosylase, OGG1, creating an AP site. Due to OGG1 activity as a type II glycosylase, OGG1 is capable of cleaving the AP site directly. However, under normal circumstances, APE1/APE2 come in and cut, cleaving the AP site, which is repaired either through short patch or long patch BER via PARP1 and XRCC1 scaffold protein that recruit appropriate proteins (i.e., Pol β) necessary for repair. APE1/APE2 both provide proofreading for pol-β to prevent errors in repair (37). APE1 provides most of the endonuclease activity compared with APE2, which provides some endonuclease activity and a large amount of exonuclease activity (36). Methoxyamine permanently modifies the AP site preventing PARP1 and other necessary proteins from accessing and fixing SSBs. These SSBs are converted to DSBs and result in cell death.