Significant impact of divalent metal ions on the fidelity, sugar selectivity, and drug incorporation efficiency of human PrimPol

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• 作者：E. John Tokarsky^a ; ^b ; Petra C. Wallenmeyer^a ; Kenneth K. Phi^a ; Zucai Suo^a ; ^b ; ^{suo.3@osu.edu}
• 关键词：(&minus ; )3TC ; (&minus ; )-β-L-2&prime ; -3&prime ; -dideoxy-3&prime ; -thiacytidine ; (&minus ; )3TC-TP ; 5&prime ; -triphosphate of (&minus ; )3TC or lamivudine ; (&minus ; )FTC ; (&minus ; )-β-L-2&prime ; -3&prime ; -dideoxy-5-fluoro-3&prime ; -thiacytidine ; (&minus ; )FTC-TP ; 5&prime ; -triphosphate of (&minus ; )FTC or emtricitabine ; AEP ; archaeo-eukaryotic primase ; dNTP ; deoxyribonucleotide ; AraCTP ; 2&prime ; -aracytidine-5&prime ; -triphosphate ; Dpo4 ; DNA polymerase IV ; GemCTP ; 2&prime ; -deoxy-2&prime ; 2&prime ; -difluorodeoxycyt
• 刊名：DNA Repair
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：49
• 期：Complete
• 页码：51-59
• 全文大小：813 K
• 卷排序：49

文摘

Human PrimPol binds DNA with a 34-fold higher affinity with Mn2+ than with Mg2+. PrimPol incorporates correct dNTPs with 100-fold higher efficiency with Mn2+ than with Mg2+. The substitution fidelity of PrimPol is 100–1000 fold lower with Mn2+ than with Mg2+. The sugar selectivity of PrimPol is 57–1800 with Mn2+ and 150–4500 with Mg2+. PrimPol incorporates cytarabine and gemcitabine, but not emtricitabine and lamivudine.