Human DNA primase uses Watson-Crick hydrogen bonds to distinguish between correct and incorrect nucleoside triphosphates

Biochemistry
Chad L MooreRobert D Kuchta

Abstract

Human DNA primase synthesizes short RNA primers that DNA polymerase alpha further elongates. Primase readily misincorporates the natural NTPs and will generate a wide variety of mismatches. In contrast, primase exhibited a remarkable resistance to polymerizing NTPs containing unnatural bases. This included bases whose shape was almost identical to the natural bases (4-aminobenzimidazole and 4,6-difluorobenzimidazole), bases shaped very differently than a natural base [e.g., 5- and 6-(trifluoromethyl)benzimidazole], bases much more hydrophobic than a natural base [e.g., 4- and 7-(trifluoromethyl)benzimidazole], bases of similar hydrophobicity as a natural base but with the Watson-Crick hydrogen-bonding groups in unusual positions (7-beta-D-guanine), and bases capable of forming only one Watson-Crick hydrogen bond with the template base (purine and 4-aminobenzimidazole). Primase only polymerized NTP analogues containing bases capable of forming hydrogen bonds between the equivalent of both N-1 and the exocyclic group at C-6 of a purine NTP (2-fluoroadenine, 2-chloroadenine, 3-deazaadenine, and hypoxanthine) and N-3 and the exocyclic group at C-4 of a pyrimidine. These data indicate that human primase requires the formation of Wat...Continue Reading

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Citations

Jun 1, 2011·Journal of Molecular Modeling·Ivonne Otero-Navas, Jorge M Seminario
Mar 1, 2006·Biochemistry·Chithra HariharanLinda J Reha-Krantz
Jul 19, 2011·Biochemistry·Travis J LundRobert D Kuchta
Dec 7, 2007·Nucleosides, Nucleotides & Nucleic Acids·Nadja V NikolausJoachim W Engels
Jan 10, 2012·Bioorganic & Medicinal Chemistry Letters·Hamad M AlkahtaniShudong Wang
Jul 24, 2010·Neuropharmacology·Grant A Krafft, William L Klein
Dec 17, 2009·Bioorganic & Medicinal Chemistry Letters·Jeremy M TravinsJay Wrobel
Apr 12, 2014·Biochemistry·Shuangluo Xia, William H Konigsberg
Sep 8, 2009·Biochimica Et Biophysica Acta·Irene Lee, Anthony J Berdis
Jun 23, 2009·Biochimica Et Biophysica Acta·Robert D Kuchta, Gudrun Stengel
Oct 31, 2007·Current Opinion in Chemical Biology·Andrew T Krueger, Eric T Kool
May 16, 2009·Angewandte Chemie·James C DelaneyEric T Kool
Oct 27, 2005·Nucleosides, Nucleotides & Nucleic Acids·A Zivković, J W Engels

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