@article {3136455,
	title = {Nucleotide deficiency promotes genomic instability in early stages of cancer development},
	journal = {Cell},
	volume = {145},
	year = {2011},
	month = {2011 Apr 29},
	pages = {435-46},
	abstract = {Chromosomal instability in early cancer stages is caused by stress on DNA replication. The molecular basis for replication perturbation in this context is currently unknown. We studied the replication dynamics in cells in which a regulator of S phase entry and cell proliferation, the Rb-E2F pathway, is aberrantly activated. Aberrant activation of this pathway by HPV-16 E6/E7 or cyclin E oncogenes significantly decreased the cellular nucleotide levels in the newly transformed cells. Exogenously supplied nucleosides rescued the replication stress and DNA damage and dramatically decreased oncogene-induced transformation. 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. Our results suggest a model for early oncogenesis in which uncoordinated activation of factors regulating cell proliferation leads to insufficient nucleotides that fail to support normal replication and genome stability.},
	keywords = {Cyclin E, DNA Replication, E2F Transcription Factors, Genomic Instability, Humans, Loss of Heterozygosity, Neoplasms, Nucleotides, Oncogene Proteins, Viral, Papillomavirus E7 Proteins, Repressor Proteins, Retinoblastoma Protein, S Phase},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2011.03.044},
	author = {Bester, Assaf C and Roniger, Maayan and Oren, Yifat S and Im, Michael M and Sarni, Dan and Chaoat, Malka and Bensimon, Aaron and Zamir, Gideon and Shewach, Donna S and Kerem, Batsheva}
}
