Inhibition of DNA methyltransferase inhibits DNA replication

被引:65
作者
Knox, JD
Araujo, FD
Bigey, P
Slack, AD
Price, GB
Zannis-Hadjopoulos, M
Szyf, M
机构
[1] McGill Univ, Ctr Canc, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada
[2] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada
关键词
D O I
10.1074/jbc.C900894199
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ectopic expression of DNA methyltransferase transforms vertebrate cells, and inhibition of DNA methyltransferase reverses the transformed phenotype by an unknown mechanism. me tested the hypothesis that the presence of an active DNA methyltransferase is required for DNA replication in human non-small cell lung carcinoma A549 cells. We show that the inhibition of DNA methyltransferase by two novel mechanisms negatively affects DNA synthesis and progression through the cell cycle, Competitive polymerase chain reaction of newly synthesized DNA shows decreased origin activity at three previously characterized origins of replication following DNA methyltransferase inhibition. We suggest that the requirement of an active DNA methyltransferase for the functioning of the replication machinery has evolved to coordinate DNA replication and inheritance of the DNA methylation pattern.
引用
收藏
页码:17986 / 17990
页数:5
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