Changes in the size of pulse-labelled DNA fragments induced in human cells by inhibitors of uracil-DNA glycosylase and DNA methylation.
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.
Aprelikova
O N
ON
Institute of Cytology, Academy of Sciences, Leningrad, U.S.S.R..
Golubovskaya
V M
VM
Kusmin
I A
IA
Tomilin
N V
NV
D004247:DNA / Q000378:metabolism*; D045647:DNA Glycosylases; D005001:Ethionine / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008745:Methylation; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D051981:Uracil-DNA Glycosidase
D004247:DNA; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; D005001:Ethionine