Herpes simplex virus-1 primase: a polymerase with extraordinarily low fidelity

Biochemistry
Kathryn A Ramirez-Aguilar, Robert D Kuchta

Abstract

We utilized templates of defined sequence to investigate the fidelity and mechanism of NTP misincorporation by DNA primase from herpes simplex virus-1. Herpes primase generated a wide range of mismatches during primer synthesis, including purine-purine, pyrimidine-pyrimidine, and purine-pyrimidine mismatches, and could even polymerize consecutive incorrect NTPs. Polymerization of noncognate NTPs resulted from primase misreading the template, as opposed to a primer slippage or dislocation mutagenesis mechanism. Primase did not efficiently misincorporate NTPs during the initiation reaction (i.e., dinucleotide synthesis). However, during primer elongation (after dinucleotide formation), herpes primase was extraordinarily inaccurate. It misincorporated NTPs at frequencies as high as 1 in 7, although frequencies of 1 in 25 to 1 in 60 were more common. In every case, however, misincorporation frequencies were no less than 1 in 100. For a specific mismatch, the DNA sequences flanking the site where misincorporation occurred could influence the frequency of misincorporation. This remarkably low level of fidelity is as low as that observed for the least accurate members of the Y class DNA polymerases involved in lesion bypass. Thus, her...Continue Reading

Citations

Aug 5, 2008·Biochemistry·Kristopher E KellerRobert D Kuchta
Mar 3, 2011·The Journal of Biological Chemistry·Isabella MuylaertPer Elias
Jul 19, 2011·Biochemistry·Travis J LundRobert D Kuchta
Sep 8, 2009·Biochimica Et Biophysica Acta·Irene Lee, Anthony J Berdis
Jun 26, 2015·Nucleic Acids Research·Thomas A GuilliamAidan J Doherty

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