Effects of the anticancer drug cis-diamminedichloroplatinum(II) on the activities of calf thymus DNA polymerase epsilon.
Effects of the anticancer drug cis-diamminedichloroplatinum(II) on the activities of calf thymus DNA polymerase epsilon.
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抗癌药物顺式二氯二氨铂(II)对小牛胸腺DNA聚合酶ε活性的影响。
DOI：
10.1021/bi00054a015
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发表时间：
1993
期刊：
影响因子：
2.9
通讯作者：
Bambara,RA
中科院分区：
文献类型：
--
作者：
Huang,L;Turchi,JJ;Wahl,AF;Bambara,RA
Revised Manuscript Received October 13, 1992 abstract: DNA polymerase (pol) t is essential for DNA replication and is thought to be a component of DNA repair systems in eukaryotic cells. Theactivities of pol e have been examined using a series of synthetic oligonucleotides designed with cis-diamminedichloroplatinum (II)(cis-DDP)-modified specific guanine residues. Pol t was incapable of synthesis over cis-DDP-modified single guanine or adjacent guanine residues present in the template strand. Both single and double guanines modified by cis-DDP present at the 3'-OH end of a primer strand completely inhibited the synthetic activity of pol e and, in addition, sequestered pol e at the platinated 3'-OH termini. The sequestering of pol e on cis-DDP modified DNA may interferewith the function of this enzymein DNA repair invivo. The intrinsic 3'to 5'proofreading exonuclease activity of pol e was also examined. Pol c was capable of degrading a single-strand template with internal cis-DDP-modified guanines up to, but not through, the platinated nucleotides. A single platinated guanosine was sufficient to block the 3'to 5'exonuclease activity of pol e. These results suggest that cis-DDP-DNA adducts inhibit DNA synthesis mediated by DNA polymerase «and that platinated sites can arrest the nuclease of pol t, a function exhibited during DNA repair. cis-Diamminedichloroplatinum (II)(cis-DDP, 1 cisplatin) is one of the most widely used anticancer drugs for treatment of solid tumors (Rosenberg, 1985; Loehrer & Einhorn, 1984). However, in some cases, after initially successful response to the drug, resistance to cis-DDP develops in the tumor cells (de Graeff et al., 1988; Scanlon et al., 1989b; Andrews & Howell, 1990). A considerable amount of evidence indicates that althoughadducts between cis-DDP and protein, or cis-DDP and RNA, exist, cis-DDP exhibits its pharmacological activity by adducting to DNA, with resulting inhibition of DNA metabolism (Harder et al., 1976; Sherman & Lippard, 1987). The cis-DDP-DNA adducts formed are predominantly intrastrand cross-links between N7 atoms of adjacent guanines (60-65%), between adenine and guanine bases (20—25%), and between two guanines separated by one nucleotide (3-7%). Interstrand cross-links between guanine bases (~ 1%) and monoadducts (~ 2%) are also present (Eastman, 1983; Dijt et al., 1988; Fichtinger-Schepman et al., 1985; Schaller et al., 1987).
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小牛胸腺中两种形式的 DNA 聚合酶 epsilon 之间的结构关系。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Siegal,G;Turchi,JJ;Jessee,CB;Mallaber,LM;Bambara,RA;Myers,TW
通讯作者：
Myers,TW
小牛胸腺 DNA 聚合酶 δ 不依赖于增殖细胞核抗原 (PCNA)
DOI：
--
发表时间：
1989
期刊：
影响因子：
--
作者：
F. Focher;M. Gassmann;Peter Hafkmeyer;E. Ferrari;S. Spadari;U. Hübscher
通讯作者：
U. Hübscher
HeLa 和小牛胸腺 DNA 聚合酶 epsilon 催化核心的鉴定和胰蛋白酶切割。
影响因子：
4.8
作者：
T. Kesti;J. Syväoja
通讯作者：
J. Syväoja
使用迁移位移凝胶电泳分析顺铂损伤的 DNA 上的 UvrABC 核酸内切酶反应中间体。
影响因子：
4.8
作者：
R. Visse;M. de Ruijter;G. Moolenaar;P. Van de Putte
通讯作者：
P. Van de Putte
影响因子：
11.2
作者：
R. Sabatino;T. Myers;R. Bambara
通讯作者：
R. Sabatino;T. Myers;R. Bambara