Dantzer F, Ménissier-de Murcia J, Barlow C, Wynshaw-Boris A, de Murcia G
Laboratoire conventionné avec le Commissariat à l'Energie Atomique, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch-Graffenstaden, France.
Carcinogenesis. 1999 Jan;20(1):177-80. doi: 10.1093/carcin/20.1.177.
Poly(ADP-ribose) polymerase (PARP) is a constitutive factor of the DNA damage surveillance network in dividing cells. Based on its capacity to bind to DNA strand breaks, PARP plays a regulatory role in their resolution in vivo. ATM belongs to a large family of proteins involved in cell cycle progression and checkpoints in response to DNA damage. Both proteins may act as sensors of DNA damage to induce multiple signalling pathways leading to activation of cell cycle checkpoints and DNA repair. To determine a possible relationship between PARP and ATM, we examined the PARP response in an ATM-null background. We demonstrated that ATM deficiency does not affect PARP activity in human cell lines or Atm-deficient mouse tissues, nor does it alter PARP activity induced by oxidative damage or gamma-irradiation. Our results support a model in which PARP and ATM could be involved in distinct pathways, both effectors transducing the damage signal to cell cycle regulators.
聚（ADP - 核糖）聚合酶（PARP）是分裂细胞中DNA损伤监测网络的组成因子。基于其与DNA链断裂结合的能力，PARP在体内对其修复过程中发挥调节作用。ATM属于参与细胞周期进程和应对DNA损伤时检查点的一大类蛋白质。这两种蛋白质都可能作为DNA损伤的传感器，诱导多种信号通路，导致细胞周期检查点激活和DNA修复。为了确定PARP与ATM之间的可能关系，我们在ATM基因缺失的背景下检测了PARP的反应。我们证明，ATM缺陷不影响人类细胞系或Atm缺陷小鼠组织中的PARP活性，也不改变由氧化损伤或γ射线照射诱导的PARP活性。我们的结果支持一种模型，其中PARP和ATM可能参与不同的途径，两者都是将损伤信号转导至细胞周期调节因子的效应器。
