Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
Chem Res Toxicol. 2024 Feb 19;37(2):216-219. doi: 10.1021/acs.chemrestox.3c00377. Epub 2024 Jan 17.
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.
组蛋白在无嘌呤/无嘧啶（AP）位点催化 DNA 链切口，同时在 3'-末端形成可逆但长寿命的 DNA-蛋白质交联（3'-组蛋白-DPCs）。然而，3'-组蛋白-DPCs 的化学结构尚未得到很好的表征，它们是否在细胞中形成也不确定。在这项研究中，我们开发了一种液相色谱串联质谱工作流程来表征组蛋白与 AP 位点反应产生的 DPCs，并希望报告组蛋白通过席夫碱与切口 AP 位点交联的证据。我们还首次证明 3'-组蛋白-DPCs在内源性产生于人胚肾 293T 细胞。
