Apurinic/Apyrimidinic Endonuclease-1 (APE1) is an abundant protein in the base excision repair pathway with the major function of hydrolyzing the phosphodiester bond on the 5’ side of an abasic site (AP) in duplex, and to a lesser extent, single-stranded DNA. We show that APE1 binds with low nM affinity to G-quadruplexes (G4s) although its cleavage activity is highly attenuated. Binding data was obtained using a novel second harmonic generation (SHG) spectroscopy method that indicated binding to an AP-containing G4 was tighter than to the same sequence in a duplex context. Indeed, this strong binding drives the refolding of duplex to quadruplex DNA when an AP site is present in a G-rich strand. Implications for this behavior in terms of the interplay of base excision repair and gene expression will be discussed.

AP-endonuclease-1 is a G-quadruplex chaperone

ACS Spring Meeting 2021

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