The mechanisms by which mitotic entry is prevented in response to DNA damage are similar to those in the G1/S checkpoint. DNA damage triggers the activation of the aforementioned ATM/ATR pathway, in which ATM/ATR phosphorylate and activate the Chk1/Chk2 checkpoint kinases. Chk1/2 phosphorylate cdc25 which, in addition to being inhibited, is also sequestered in the cytoplasm by the 14-3-3 proteins. 14-3-3 are upregulated by p53, which, as previously mentioned, is activated by Chk1 and ATM/ATR. p53 also transactivates p21, and both p21 and the 14-3-3 in turn inhibit cyclin B-cdc2 complexes through the phosphorylation and cytoplasmic sequestering of cdc2. In addition, the inactivation of cdc25 results in its inability to dephosphorylate and activate cdc2. Finally, another mechanism of damage response is through the negative regulation of Plk1 by ATM/ATR, which in turn results in the stabilization of Wee1 and Myt1, which can then phosphorylate and inhibit cdc2, thus keeping the cell arrested in G2 until the damage is fixed.