The members of the CDC25 family, CDC25A, CDC25B, and CDC25C, activate the cyclin-dependent kinases at different points in the cell cycle by dephosphorylating key proteins. The ~65 kDa CDC25A protein is a tyrosine phosphatase that regulates the G1/S transition by activating cyclin E/Cdk2 and cyclin A/Cdk2 complexes, which are required for DNA synthesis. CDC25A acts as a checkpoint to prevent DNA replication following DNA damage. DNA damage induces phosphorylation of CDC25A, resulting in its rapid degradation via the ubiquitin-proteosome pathway, and thus silencing Cdk2 activity.