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

作　　者：孟祥兵 董燕 孙志贤 

出　　处：《Science China(Life Sciences)》1999年第4期427-434,共8页中国科学（生命科学英文版）

基　　金：Project supported by the National Natural Science Foundation of China (Grant No. 39700038).

摘　　要：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 surveillance, p21as/MCF-7 cells stably transfected by p21 antisense expression plasmid pC-WAFl-AS and Gadd45as/MCF-7 stably transfected by Gadd45 antisense expression plasmid pCMVas45 were established. It was observed that G1 arrest induced by radiation was significantly reduced in Gadd45as/MCF-7 cells as well as in p21as/MCF-7 cells. Repair of radiation damaged report gene greatly reduced in Gadd45asMCF-7 and p21as/MCF-7 cells. Apoptosis significantly increased in p21as/MCF-7 after exposure to radiation. These results suggest that both p21 and Gadd45 support cellular survival by taking roles in G1 arrest and DNA repair, furthermore, p21 protects cells from death by inhibiting apoptosis after exposure to ionizing radiation.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 surveillance, 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 G₁ arrest induced by radiation was significantly reduced in Gadd45^as/MCF-7 cells as well as in p21^as/MCF-7 cells. Repair of radiation damaged report gene greatly reduced in Gadd45^as/MCF-7 and p21^as/MCF-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 G₁ arrest and DNA repair, furthermore, p21 protects cells from death by inhibiting apoptosis after exposure to ionizing radiation.

关 键 词：P21 GADD45 G1 ARREST DNA repair apoptosis. 

分 类 号：R346[医药卫生—基础医学]