Unformatted text preview: er development . A Model for the Events Leading to Genomic Instability in Early Stages of Cancer Development e expression forces cell proliferation by aberrant activation of cell-cycle regulators (Rb-E2F). Insufﬁcient activation of the nucleotid
s results in a low-nucleotide pool that fails to support normal DNA replication. This leads to replication stress and promotes genomic in
ges of cancer development. Additional factors contribute to genomic instability in different stages of tumorigenesis, such as reactive
lomere loss, hypoxia, abrogated mitotic checkpoints, and loss of the DNA damage response (DDR). ensive proliferation of the cells, leading to replicationDNA damage and increased tumorigenicity. As a result, DNA replication starts with a low-nuc
leading to replication stress and DNA damage. Our Why does inac-va-on of Rb lead to cancer? • Ac7va7on of E2Fs lead to replica7on stress which causes genomic instability • Replica7on stress arises...
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- Fall '14
- DNA, DNA Damage