Negishi K, Takahashi M, Yamashita Y, Nishizawa M, Hayatsu H
Biochemistry. 1985 Dec 3;24(25):7273-8. doi: 10.1021/bi00346a038.
N4-Aminocytidine is a potent mutagen toward Escherichia coli and Salmonella typhimurium. It induced reversion of an amber mutant of phi X174 phage (am3) to the wild type. This reversion was shown to be exclusively due to the AT to GC transition. It is likely that N4-aminocytidine is metabolized within the bacterial cells into N4-aminodeoxycytidine 5'-triphosphate and this nucleotide is incorporated into DNA during the multiplication of the cells and the phages, thereby causing base-pair transitions. The molecular basis for this erroneous replication was obtained in studies of in vitro incorporation of N4-aminodeoxycytidine 5'-triphosphate into polynucleotides catalyzed by the E. coli DNA polymerase I large fragment. The results have shown that this cytosine analogue can be efficiently incorporated as a substitute of cytosine and that it can also be incorporated as a substitute of thymine. The ratio in the rate of the N4-aminocytosine nucleotide incorporation to that of natural nucleotide incorporation was 1/2 to cytosine and 1/30 to thymine. Furthermore, the N4-aminocytosine residues in the polynucleotide templates can be read by the enzyme as efficiently as cytosines, and guanines were incorporated opposite to them.
N4-氨基胞苷对大肠杆菌和鼠伤寒沙门氏菌是一种强效诱变剂。它能诱导φX174噬菌体（am3）的琥珀突变体回复为野生型。这种回复被证明完全是由于AT到GC的转变。N4-氨基胞苷很可能在细菌细胞内代谢为N4-氨基脱氧胞苷5'-三磷酸，并且这种核苷酸在细胞和噬菌体增殖过程中掺入DNA，从而导致碱基对转变。这种错误复制的分子基础是在对大肠杆菌DNA聚合酶I大片段催化的N4-氨基脱氧胞苷5'-三磷酸体外掺入多核苷酸的研究中获得的。结果表明，这种胞嘧啶类似物可以作为胞嘧啶的替代物被有效掺入，也可以作为胸腺嘧啶的替代物被掺入。N4-氨基胞嘧啶核苷酸掺入速率与天然核苷酸掺入速率之比，对胞嘧啶为1/2，对胸腺嘧啶为1/30。此外，多核苷酸模板中的N4-氨基胞嘧啶残基可以被该酶像胞嘧啶一样有效地识别，并且鸟嘌呤会与之配对掺入。
