Figure 7.
Model for p53 stabilization in response to DNA damage and stalled replication. IR, induces DNA DSBs and activates Chk2/hCds1 in an ATM-dependent manner. Thymine dimers, which are induced by UV light and stalled replication, activate Chk2/hCds1 in an ATM-independent manner. Stabilization of p53 in response to UV light is dependent on ATR and requires DNA replication, suggesting that ATR signals the presence of thymine dimers and/or replication blocks to Chk2/hCds1 (? indicates that it is not known whether ATR responds to thymine dimers or stalled replication or both). In budding yeast, activation of RAD53/SPK1 (the Chk2/hCds1 homolog) is dependent on MEC1 (the ATM and ATR homolog) and leads to phosphorylation of the SWI6 transcription factor and G1 arrest.