Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase
Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase
复制标题
DOI：
10.1128/mcb.02248-06
复制
发表时间：
2007-08-01
影响因子：
5.3
通讯作者：
Caldecott, Keith W.
中科院分区：
文献类型：
--
作者：
Fisher, Anna E. O.;Hochegger, Helfrid;Caldecott, Keith W.
单链断裂是细胞中最常见的损伤，其修复缺陷与神经退行性疾病有关。在单链断裂修复（SSBR）过程中最早的事件之一是聚（ADP-核糖）聚合酶（PARP）快速合成聚（ADP-核糖）（PAR），随后其被聚（ADP-核糖）糖水解酶（PARG）快速降解。虽然聚（ADP-核糖）的合成对于染色体SSBR的快速速率是重要的，但聚（ADP-核糖）聚合酶1（PARP-1）和PARP-2以及PARG随后降解PAR的相对重要性尚不清楚。在这里，我们已经定量了在去除PARP-1、PARP-2和PARG的人A549细胞中的SSBR率，无论是单独还是组合。我们报告说，虽然PARP-1对于人类A549细胞中SSBR的快速全球速率至关重要，但即使在PARP-1水平耗尽的情况下，PARP-2的耗尽也只有很小的影响。此外，我们将PARG确定为SSBR的一种新颖且关键的组分，它与PARP-1一起加速了这一过程。
Single-strand breaks are the commonest lesions arising in cells, and defects in their repair are implicated in neurodegenerative disease. One of the earliest events during single-strand break repair (SSBR) is the rapid synthesis of poly(ADP-ribose) (PAR) by poly(ADP-ribose) polymerase (PARP), followed by its rapid degradation by poly(ADP-ribose) glycohydrolase (PARG). While the synthesis of poly(ADP-ribose) is important for rapid rates of chromosomal SSBR, the relative importance of poly(ADP-ribose) polymerase 1 (PARP-1) and PARP-2 and of the subsequent degradation of PAR by PARG is unclear. Here we have quantified SSBR rates in human A549 cells depleted of PARP-1, PARP-2, and PARG, both separately and in combination. We report that whereas PARP-1 is critical for rapid global rates of SSBR in human A549 cells, depletion of PARP-2 has only a minor impact, even in the presence of depleted levels of PARP-1. Moreover, we identify PARG as a novel and critical component of SSBR that accelerates this process in concert with PARP-1.