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DNA methylation has a role in the regulation of gene expression during normal mammalian development but can also mediate epigenetic silencing of CpG island genes in cancer and other diseases. Many individual genes (including tumor suppressors) have been shown to undergo de novo methylation in specific tumor types, but the biological logic inherent in this process is not understood. To decipher this mechanism, we have adopted a new approach for detecting CpG island DNA methylation that can be used together with microarray technology. Genome-wide analysis by this technique demonstrated that tumor-specific methylated genes belong to distinct functional categories, have common sequence motifs in their promoters and are found in clusters on chromosomes. In addition, many are already repressed in normal cells. These results are consistent with the hypothesis that cancer-related de novo methylation may come about through an instructive mechanism. [ABSTRACT FROM AUTHOR]

Evaluates the hypothesis that vertebrate cells possess mechanisms that protect them from epigenomic stress similar to DNA damage checkpoints. Effect of DNA methyltransferase knockdown by an oligonucleotide antisense on the intra-S-phase arrest of DNA replication; Implication on the arrest of cells at different positions throughout the S-phase of the cell cycle; Proposition on intra-S-phase arrest of DNA replication.