Cell Cycle Checkpoints

In the G1 phase there are two types of DNA damage responses, the p53-dependent and the p53-independ-ent pathways. The p53-dependent responses inhibit CDKs through the up-regulation of genes encoding CKIs mediated by the p53 protein, whereas the p53-independent mechanisms inhibit CDKs through the inhibitory T14Y15 phosphorylation of Cdk2. Failure of DNA damage checkpoints in G1 leads to mutagen-ic replication of damaged templates and other replication defects.