Mass Spectrometry Evidence for Forming Schiff Base 3'-DNA-Histone Cross-Links from Abasic Sites and in Human Cells.

Chem Res Toxicol

Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.

Published: February 2024

Histones catalyze DNA strand incision at apurinic/apyrimidinic (AP) sites accompanied by the formation of reversible but long-lived DNA-protein cross-links at 3'-termini (3'-histone-DPCs). However, the chemical structures of 3'-histone-DPCs are not well characterized, and whether they are formed in cells is uncertain. In this study, we developed a liquid chromatography with tandem mass spectrometry workflow to characterize DPCs produced from the reaction of histones with AP sites and wish to report evidence that histones cross-link to incised AP sites via Schiff bases. We also demonstrated for the first time that 3'-histone-DPCs are produced endogenously in human embryonic kidney 293T cells.

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http://dx.doi.org/10.1021/acs.chemrestox.3c00377DOI Listing

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