Regulation of G₂/M cell cycle DNA damage checkpoints

Deregulation of the cell cycle checkpoints is a key step in tumorigenesis. we present evidence that apart from CDC25, WEE1 may also be important for the G₂/M DNA damage checkpoints. ING1 is a candidate tumor suppressor that cooperates with p53 to inhibit cell proliferation. We show that ING1 can regulate the cell cycle and the DNA damage responses at G₂/M phase independent of p53 functions. ING1b enhanced the p53-independent G₂/M DNA damage checkpoint induced by adriamycin, but did not affect the G₁ DNA damage checkpoint. No significant transactivation of p21^CIP1/WAF1 and MDM2 by ING1 in the absence of p53 was observed, suggesting that mechanisms involving activation of p53-related proteins are unlikely to contribute to the G₂/M cell cycle arrest caused by ING1b. These data provide evidence of the involvement of WEE1 and ING1 in the G₂/M DNA damage checkpoint. Understanding precisely how these proteins regulate the cell cycle and checkpoints may shed light on the mechanism of tumorigenesis