In Vitro Bypass Replication of the Cisplatin-d(GpG) Lesion by Calf Thymus DNA Polymerase β and Human Immunodeficiency Virus Type I Reverse Transcriptase Is Highly Mutagenic*

In Vitro Bypass Replication of the Cisplatin-d(GpG) Lesion by Calf Thymus DNA Polymerase β and Human Immunodeficiency Virus Type I Reverse Transcriptase Is Highly Mutagenic*
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小牛胸腺 DNA 聚合酶 β 和人类免疫缺陷病毒 I 型逆转录酶对顺铂-d(GpG) 损伤的体外旁路复制具有高度诱变性*

DOI:
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发表时间:
1996
影响因子:
4.8
通讯作者:
G. Villani
G. Villani
中科院分区:
生物学2区
文献类型:
--
作者:
J. Hoffmann;M. Pillaire;D. Garcia;S. Lapalu;G. Villani

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Eukaryotic DNA polymerase β and the reverse transcriptases are the most inaccurate of the known DNA polymerases. We report here mutagenic replication in vitro past intrastrand N(7)G-N(7)G chelates of the cis-diamminedichloroplatinum(II), the major DNA adduct of the antitumor agent cisplatin by calf thymus DNA polymerase β and human immunodeficiency virus type I reverse transcriptase (42% and 26% mutations, respectively). The most frequent modifications generated by both enzymes were one-base frameshift deletions. Only one mutational hot spot opposite the platinated guanines was observed with human immunodeficiency virus type I reverse transcriptase, while two hot spots were generated by DNA polymerase β, one at the base situated 5′ to the lesion and the other situated 4–6 nucleotides 5′ to the adduct. An unusual mutagenic event, tandem replication of a 12-base pair sequence, was observed with DNA polymerase β. The mutational spectra of the two DNA polymerases suggest that template slippage occurred with higher frequency in the presence of the more distributive DNA polymerase β.
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