Y-Box-Binding Protein 1 Stimulates Abasic Site Cleavage

Biochemistry. Biokhimii︠a︡
E E AlemasovaO I Lavrik

Abstract

Apurinic/apyrimidinic (AP) sites are among the most frequent DNA lesions. The first step in the AP site repair involves the magnesium-dependent enzyme AP endonuclease 1 (APE1) that catalyzes hydrolytic cleavage of the DNA phosphodiester bond at the 5' side of the AP site, thereby generating a single-strand DNA break flanked by the 3'-OH and 5'-deoxyribose phosphate (dRP) groups. Increased APE1 activity in cancer cells might correlate with tumor chemoresistance to DNA-damaging treatment. It has been previously shown that the multifunctional oncoprotein Y-box-binding protein 1 (YB-1) interacts with APE1 and inhibits APE1-catalyzed hydrolysis of AP sites in single-stranded DNAs. In this work, we demonstrated that YB-1 stabilizes the APE1 complex with double-stranded DNAs containing the AP sites and stimulates cleavage of these AP sites at low magnesium concentrations.

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Citations

Nov 30, 2018·Journal of Biomolecular Structure & Dynamics·Anton V EndutkinDmitry O Zharkov
Sep 16, 2020·International Journal of Radiation Oncology, Biology, Physics·Konstanze LettauMahmoud Toulany

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