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Comment
. 2017 Mar 14;114(11):2788-2790.
doi: 10.1073/pnas.1701244114. Epub 2017 Mar 6.

G-quadruplex-forming promoter sequences enable transcriptional activation in response to oxidative stress

Bogdan I Fedeles  1   2
Affiliations
Comment

G-quadruplex-forming promoter sequences enable transcriptional activation in response to oxidative stress

Bogdan I Fedeles. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Fig. 1.
Fig. 1.
The ability of ROS generated during aerobic metabolism, hypoxia, or oxidative stress to turn on the expression of certain genes has been previously documented. However, the mechanistic details of this process are unclear. In PNAS, Fleming et al. describe a mechanism by which oxidative DNA damage can activate transcription of genes (e.g., VEGF, NTHL1) that contain potential G-quadruplex (G4)–forming sequences with five G tracks in their promoters. ROS damage in the G-rich regions of the promoter generates 8-oxoguanine, which is removed by the BER glycosylase OGG1 to form an AP site. The rearrangement of the DNA strand into a G4 structure prevents APE1 lyase, the second BER enzyme, to access the AP site. However, a more stable G4 can form by involving the fifth G track and looping out the AP site, which can now be bound by APE1. Through its regulatory domains, APE1 then recruits transcription factors to initiate transcription.
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