中文摘要：

cyclin 依赖的 kinase 禁止者 p21WAF1/Cip1 是 translocates 损坏回答进原子核在 DNA 期间参予 DNA 修理的一个批评房间周期管理者。在现在的学习，我们证明肿瘤 suppressor， promyelocytic 白血病蛋白质(PML ) 在一条 p53 独立的小径贡献 p21 的起来规定。在 p53 空的 H1299 和 HCT 116 (p53/) 的 PML 击倒由特定的 siRNA 的肿瘤房间在 p21 蛋白质半衰期导致了 p21 蛋白质表示， -irradiation-induced p21 起来规定的抑制，和减少的下面规定。在 PML 击倒的 H1299 房间， p21 蛋白质表示的下面规定被显示 p21 蛋白质的 proteasomal 降级被增加的 MG132 处理颠倒。因此， PML 断然由禁止调停 proteasome 的解朊作用调整 p21 表示。PML 击倒减少两倍海滨打破的 -irradiation-induced (DSB ) 的修理是由在 p21 和增殖的房间之间的 -H2AX foci 和一个减少的协会的推迟的消失显示了原子抗原(PCNA ) 。p21 的在表示上显著地恢复了推迟的 DSB 修理功能。一起拿，这些数据在 -irradiation-induced DNA 损坏回答为在 PML 和 p21 之间的一种 p53 独立的功能的关系提供证据，并且在 p53 缺乏的肿瘤房间作为 p21 的一个积极 translational 以后管理者识别 PML。

英文摘要：

The cyclin-dependent kinase inhibitor p21wAF1/cipl is a critical cell cycle regulator which translocates into the nucleus to participate in DNA repair during DNA damage responses. In the present study, we showed that the tumor suppressor, promyelocytic leukemia protein （PML） contributes to the up-regulation of p21 in a p53-independent pathway. Knock-down of PML in p53-null H1299 and HCT 116 （p53-/） tumor cells by specific siRNA resulted in down-regulation of p21 protein expression, inhibition of γ-irradiation-induced p21 up-regulation, and a decrease in p21 protein half-life. In PML knockdown H1299 cells, the down-regulation of p21 protein expression was reversed by MG132 treatment indicating that the proteasomal degradation of p21 protein was increased. Thus, PML positively regulates p21 expression by inhibiting proteasome-mediated proteolysis. Knockdown of PML decreased the repair of y-irradiation-induced double strand breaks （DSBs） as indicated by the delayed disappear- ance of ＂/-H2AX foci and a decreased association between p21 and proliferating cell nuclear antigen （PCNA）. Over-expression of p21 significantly restored the delayed DSB repair function. Taken together, these data provide evidence for a p53-independent functional relationship between PML and p21 in y-irradiation-induced DNA damage responses, and identify PML as a positive post-translational regulator of p21 in p53-deficient tumor cells.