Nucleotide Deficiency Promotes Genomic Instability in Early Stages of Cancer Development

  title={Nucleotide Deficiency Promotes Genomic Instability in Early Stages of Cancer Development},
  author={Assaf C. Bester and Maayan Roniger and Yifat S. Oren and Michael M. Im and Dan Sarni and Malka Chaoat and Aaron Bensimon and Gideon Zamir and Donna S. Shewach and Batsheva Kerem},
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… CONTINUE READING
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Bcl2 induces DNA replication stress by inhibiting ribonucleotide reductase.

Cancer research • 2014
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