Local DNA damage by proton microbeam irradiation induces poly(ADP-ribose) synthesis in mammalian cells.
Local DNA damage by proton microbeam irradiation induces poly(ADP-ribose) synthesis in mammalian cells.
复制标题
质子微束照射造成的局部 DNA 损伤会诱导哺乳动物细胞中聚 (ADP-核糖) 的合成。
作者：
L. Tartier;C. Spenlehauer;H. C. Newman;M. Folkard;K. Prise;B. Michael;J. Ménissier;G. de Murcia
电离辐射（IR）诱导损伤的细胞恢复涉及聚（ADP-核糖）聚合酶（PARP-1和PARP-2）活性，导致诱导负责维持基因组完整性的信号网络。在目前的工作中，带电粒子微束提供3.2 MeV的质子从货车德格拉夫加速器已被用来局部照射哺乳动物细胞。我们显示PARP对局部照射的立即反应，伴随着ATM和Rad 51在DNA损伤位点的招募，这两种蛋白质都参与DNA链断裂修复。我们发现两个DNA损伤依赖性翻译后修饰，即核蛋白的聚（ADP-核糖基）化和组蛋白H2 AX的磷酸化之间存在共定位，但没有联系。然而，它们两者都应该被认为是活细胞中IR损伤的真正的即时敏感标记物。因此，该技术提供了一种强有力的方法，旨在了解源自DNA损伤位点的信号与随后的DNA链断裂修复机制激活之间的相互作用
Cellular recovery from ionizing radiation (IR)-induced damage involves poly(ADP-ribose) polymerase (PARP-1 and PARP-2) activity, resulting in the induction of a signalling network responsible for the maintenance of genomic integrity. In the present work, a charged particle microbeam delivering 3.2 MeV protons from a Van de Graaff accelerator has been used to locally irradiate mammalian cells. We show the immediate response of PARPs to local irradiation, concomitant with the recruitment of ATM and Rad51 at sites of DNA damage, both proteins being involved in DNA strand break repair. We found a co-localization but no connection between two DNA damage-dependent post-translational modifications, namely poly(ADP-ribosyl)ation of nuclear proteins and phosphorylation of histone H2AX. Both of them, however, should be considered and used as bona fide immediate sensitive markers of IR damage in living cells. This technique thus provides a powerful approach aimed at understanding the interactions between the signals originating from sites of DNA damage and the subsequent activation of DNA strand break repair mechanisms
影响因子：
56.9
作者：
Nelms, BE;Maser, RS;Petrini, JHJ
通讯作者：
Petrini, JHJ