N^4-アミノシチジンによる突然変異の機構

スポンサーリンク

概要

• 論文の詳細を見る

• N^4-Aminocytidine is strongly mutagenic towards E. coli, S. typhimurium, B. subtilis and coliphages φX174 and M13mp2. It also causes mutations in mammalian cell lines and somatic cell mutations in D. melanogaster. The sequence analysis of deoxyribonucleic acid (DNA) from mutated phages revealed that N^4-aminocytidine induces both adeninethymine (AT) to guanine-cytosine (GC) and GC to AT transitions. No transversions are detectable. When E. coli and the mammalian cells were cultured in the presence of [^3H]-N^4-aminocytidine, [^3H]-N^4-aminodeoxycytidine was found in their DNA. It is likely that N^4-aminocytidine is metabolized within the cells into N^4-aminodeoxycytidine 5'-triphosphate (dC^<am>TP), which is then incorporated into DNA, thereby causing base-pair transitions. To prove this hypothesis, we studied the incorporation of dC^<am>TP into polynucleotides in the in vitro DNA synthesis catalyzed by E. coli DNA polymerase I large fragment (Klenow enzyme) and DNA polymerase α from a mouse cell line. Both polymerases catalyze incorporation of dC^<am>TP into DNA efficiently in place of dCTP opposite guanine, and less efficiently, but to a significant extent, in place of dTTP opposite adenine. These observations prove the erroneous nature of dC^<am>TP as a substrate for DNA synthesis. DNA containing N^4-aminocytosine was prepared by the incorporation of dC^<am>TP into single-stranded phage DNA annealed to complementary oligonucleotides. The DNA was transfected to E. coli cells. The analysis of progeny phages indicates that N^4-aminocytosine residue in DNA causes A to G or G to A mutation in the position opposite to the site where N^4-aminocytosine should be incorporated.

• 公益社団法人日本薬学会の論文
• 1990-05-25

著者

• 根岸 和雄

  Okayama University Advanced Science Research Center:nihon Pharmaceutical University

• 根岸 和雄

  岡山大学遺伝子実験施設

関連論文

• DNAの新しい抽出法 -キトサンを用いた方法-
• 変異原性ヌクレオチド, P-nucleoside triphosphateの鋳型-プライマーへの取り込み活性
• ヌクレオシドアナログによる塩基対合異常と突然変異 (核酸化学の新展開--新しい機能性分子を求めて) -- (核酸の構造)
• Synergistic Action of Bisulfite and Dimethylsulfoxide on Bacteriophage Lambda
• 防爆形冷蔵庫
• Formation of S-[5-(2'-Deoxyuridyl)] thiol Compounds in the Dehalogenation of 5-Bromo- and 5-Iodo-2'-deoxyuridine with Cysteine Derivatives
• Oxidative DNA Damage Induced by 364-nm UVA Laser in Yeast Cells
• シトシンアナログによる塩基の誤対合と変異
• DNAシークエンサーの選び方
• N^4-アミノシチジンによる突然変異の機構

スポンサーリンク