Chk2/hCds1 functions as a DNA damage checkpoint in G₁ by stabilizing p53. This study demonstrates that Chk2/hCds1, a human homolog of yeast DNA damage checkpoint genes, stabilizes the p53 tumor suppressor protein, leading to G₁ cell cycle arrest in response to DNA damage. Chk2/hCds1 phosphorylates p53 on Ser-20, which disrupts its interaction with Mdm2, a protein that targets p53 for degradation. This phosphorylation stabilizes p53, allowing it to activate genes that induce cell cycle arrest. In vitro and in vivo experiments show that Chk2/hCds1 activates p53 and stabilizes it after DNA damage, and that this process is regulated by ATM. The study also shows that Chk2/hCds1 is involved in the DNA damage checkpoint pathway that leads to G₁ arrest. The findings suggest that Chk2/hCds1 is a key regulator of p53 stability and cell cycle arrest in response to DNA damage. The study also highlights the importance of Chk2/hCds1 in the DNA damage response pathway and its potential role in cancer development.Chk2/hCds1 functions as a DNA damage checkpoint in G₁ by stabilizing p53. This study demonstrates that Chk2/hCds1, a human homolog of yeast DNA damage checkpoint genes, stabilizes the p53 tumor suppressor protein, leading to G₁ cell cycle arrest in response to DNA damage. Chk2/hCds1 phosphorylates p53 on Ser-20, which disrupts its interaction with Mdm2, a protein that targets p53 for degradation. This phosphorylation stabilizes p53, allowing it to activate genes that induce cell cycle arrest. In vitro and in vivo experiments show that Chk2/hCds1 activates p53 and stabilizes it after DNA damage, and that this process is regulated by ATM. The study also shows that Chk2/hCds1 is involved in the DNA damage checkpoint pathway that leads to G₁ arrest. The findings suggest that Chk2/hCds1 is a key regulator of p53 stability and cell cycle arrest in response to DNA damage. The study also highlights the importance of Chk2/hCds1 in the DNA damage response pathway and its potential role in cancer development.