When a DNA damage occurs during G1 phase of the cell cycle, it activates a G1/S DNA damage checkpoint that pauses the cell cycle to allow time for DNA repair (reviewed in Shackelford et al. 1999, Poon 2016). In the G1 phase there are two types of DNA damage responses, the p53-dependent and the p53-independent pathways. The p53-dependent responses inhibit CDKs through the upregulation of genes encoding cyclin-dependent kinase inhibitors (CKIs) mediated by the TP53 transcription factor (reviewed in Shackelford et al. 1999, Poon 2016), whereas the p53-independent mechanisms inhibit CDKs through the inhibitory T14 and Y15 phosphorylation of CDK2 (reviewed in Shackelford et al. 1999). Failure of DNA damage checkpoints in G1 leads to mutagenic replication of damaged templates and other replication defects.