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. Author manuscript; available in PMC: 2013 Aug 12.
Published in final edited form as: Cell. 2011 Apr 29;145(3):435–446. doi: 10.1016/j.cell.2011.03.044

Figure 5. A Model for the Events Leading to Genomic Instability in Early Stages of Cancer Development.

Figure 5

Oncogene expression forces cell proliferation by aberrant activation of cell-cycle regulators (Rb-E2F). Insufficient activation of the nucleotide biosynthesis pathways results in a low-nucleotide pool that fails to support normal DNA replication. This leads to replication stress and promotes genomic instability during early stages of cancer development. Additional factors contribute to genomic instability in different stages of tumorigenesis, such as reactive oxygen species (ROS), telomere loss, hypoxia, abrogated mitotic checkpoints, and loss of the DNA damage response (DDR).