Aprelikova O N, Golubovskaya V M, Kusmin I A, Tomilin N V
Institute of Cytology, Academy of Sciences, Leningrad, U.S.S.R..
Mutat Res. 1989 Aug;213(2):135-40. doi: 10.1016/0027-5107(89)90144-9.
An inhibitor of uracil-DNA glycosylase, uracil, induces an increase in the size of pulse-labelled DNA fragments in human cells in vivo suggesting that dUMP incorporation into DNA and uracil-DNA glycosylase contribute to the small size of pulse-labelled DNA. It is also shown that inhibition of DNA methylation in vivo by ethionine and 5-azacytidine induces a decrease in the size of pulse-labelled DNA, and the effect is partially suppressed by uracil. In vitro experiments with purified uracil-DNA glycosylase from human placenta show that DNA hypermethylation inhibits the enzyme. The data make it possible to explain the antimutagenic effect of ethionine in mammalian cells [1] by stimulation of the repair of DNA containing incorporated uracil on the basis of the hypothesis that DNA-uracil repair stimulates mismatch correction leading to preferential excision of misincorporated nucleotides from daughter DNA strands.
尿嘧啶（一种尿嘧啶-DNA糖基化酶抑制剂）在体内可使人类细胞中脉冲标记的DNA片段大小增加，这表明dUMP掺入DNA以及尿嘧啶-DNA糖基化酶导致了脉冲标记DNA的小尺寸。研究还表明，乙硫氨酸和5-氮杂胞苷在体内对DNA甲基化的抑制会导致脉冲标记DNA大小减小，而尿嘧啶可部分抑制该效应。用人胎盘纯化的尿嘧啶-DNA糖基化酶进行的体外实验表明，DNA高甲基化会抑制该酶。基于DNA-尿嘧啶修复刺激错配校正从而导致优先从子代DNA链中切除错掺入核苷酸的假说，这些数据使得通过刺激含掺入尿嘧啶的DNA的修复来解释乙硫氨酸在哺乳动物细胞中的抗诱变作用成为可能[1]。
