Figure 2.

Destiny of cells that have experienced DNA replication stress. Cells with under‐replicated genomic regions, caused by DNA replication stress during S phase, either activate the DNA damage checkpoint before mitosis or proceed into mitosis. When the DNA damage checkpoint is properly activated, cells cease aberrant growth and induce cellular senescence or apoptosis. As the markers for the DNA damage checkpoint or cellular senescence are often detected in the precancerous lesions, this cascade is believed to constitute a barrier to malignant progression. In contrast, when the DNA damage checkpoint is abrogated, cells with under‐replicated genomic regions proceed into mitosis and induce chromosomal abnormalities, possibly caused by ultrafine bridges (UFBs). These cells display genomic instability, which contribute to malignant progression. ATM, ataxia telangiectasia mutated; Chk2, checkpoint kinase 2