Mechanism of p53 downstream effectors p21 and Gadd45 in DNA damage surveillance.

Both p21(WAF1/CIP1) and Gadd45 were activated in a p53-dependent manner in MCF-7 cells after being exposed to ionizing radiation. In order to investigate their roles in DNA damage suweillance, p21(as)/MCF-7 cells stably transfected by p21 antisense expression plasmid pC-WAF1-AS and Gadd45(as)/MCF-7 stably transfected by Gadd45 antisense expression plasmid pCMVas45 were established. It was observed that G(1) arrest induced by radiation was significantly reduced in Gadd45(as)/MCF-7 cells as well as in p21(as)/MCF7 cells. Repair of radiation damaged report gene greatly reduced in Gadd45(as)/MCF-7 and p21(as)VMCF-7 cells. Apoptosis significantly increased in p21(as)/MCF-7 after exposure to radiation. These results suggest that both p21 and Gadd45 support cellular survival by taking roles in G(1) arrest and DNA repair, furthermore, p21 protects cells from death by inhibiting apoptosis after exposure to ionizing radiation.