Sequence‐dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)‐(R)‐2‐Aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) Monohydrate

Mitsumasa Iwata, Shunji Izuta, Motoshi Suzuki, Kiyohide Kojima, Yoshihito Furuhashi, Yutaka Tomoda, Shonen Yoshida

研究成果: Article査読

11 被引用数 (Scopus)

抄録

We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (‐)‐(R)‐2‐aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) monohydrate (DWA‐2114R), a derivative of the antitumor drug cis‐ diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA‐2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose‐dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second‐strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase α were strongly arrested at guanine‐guanine sequences (GG). Stop bands were also observed at adenine‐guanine sequences (AG) guanine‐adenine‐guanine sequences (GAG) and mono‐guanine sequence (G). Calf testis DNA polymerase β was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP.

本文言語English
ページ(範囲)433-439
ページ数7
ジャーナルJapanese Journal of Cancer Research
82
4
DOI
出版ステータスPublished - 04-1991
外部発表はい

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

フィンガープリント 「Sequence‐dependent Termination of Mammalian DNA Polymerase Reaction by a New Platinum Compound, (–)‐(R)‐2‐Aminomethylpyrrolidine(1,1‐cyclobutane‐dicarboxylato)‐2‐platinum(II) Monohydrate」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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