Structural Basis for Error-Free Bypass of the 5-N-Methylformamidopyrimidine-dG Lesion by Human DNA Polymerase 畏 and Sulfolobus solfataricus P2 Polymerase IV

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• 作者：Amritraj Patra ; Surajit Banerjee ; Tracy L. Johnson Salyard ; Chanchal K. Malik ; Plamen P. Christov ; Carmelo J. Rizzo ; Michael P. Stone ; Martin Egli
• 刊名：Journal of the American Chemical Society
• 出版年：2015
• 出版时间：June 10, 2015
• 年：2015
• 卷：137
• 期：22
• 页码：7011-7014
• 全文大小：344K
• ISSN：1520-5126

文摘

Np>6p>-(2-Deoxy-pan class="smallcaps">dpan>-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine (MeFapy-dG) arises from N7-methylation of deoxyguanosine followed by imidazole ring opening. The lesion has been reported to persist in animal tissues. Previous in vitro replication bypass investigations of the MeFapy-dG adduct revealed predominant insertion of C opposite the lesion, dependent on the identity of the DNA polymerase (Pol) and the local sequence context. Here we report crystal structures of ternary Pol路DNA路dNTP complexes between MeFapy-dG-adducted DNA template:primer duplexes and the Y-family polymerases human Pol 畏 and P2 Pol IV (Dpo4) from Sulfolobus solfataricus. The structures of the hPol 畏 and Dpo4 complexes at the insertion and extension stages, respectively, are representative of error-free replication, with MeFapy-dG in the anti conformation and forming Watson鈥揅rick pairs with dCTP or dC.