Lack of DNA Building Blocks Promotes Cancer Cell Formation

Factors causing depletion of the nucleotide building blocks of DNA have been linked to the initiation of processes that cause normal cells to become cancerous.

Investigators at the Hebrew University of Jerusalem (Israel) worked with cell cultures that were put under stress when the Rb-E2F signaling pathway was aberrantly activated. Aberrant activation of this pathway by HPV-16 E6/E7 (human papillomavirus) or cyclin E oncogenes significantly decreased the cellular nucleotide levels. The cells making up these cultures were prone to transform spontaneously into cancer cells.

The investigators reported in the April 29, 2011, issue of the journal Cell that supplying exogenously nucleosides to the cell cultures eliminated the replication stress and DNA damage and dramatically decreased oncogene-induced transformation into cancer cells. Increased transcription of nucleotide biosynthesis genes, mediated by expressing the transcription factor c-myc, increased the nucleotide pool and also rescued the replication-induced DNA damage.

The authors concluded that, "This work raises the possibility for developing new approaches for protection against precancerous development, even possibly creating a kind of treatment to decrease DNA breakage.”

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Hebrew University of Jerusalem