Rapid Detection and Signaling of DNA Damage by PARP-1.

Rapid Detection and Signaling of DNA Damage by PARP-1.
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PARP-1对DNA损伤的快速检测和信号转导

DOI:
10.1016/j.tibs.2021.01.014
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发表时间:
2021-09
影响因子:
13.8
通讯作者:
Black BE
Black BE
中科院分区:
生物学1区
文献类型:
--
作者:
Pandey N;Black BE

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聚ADP核糖基聚合酶-1(Poly(ADP-ribosyl)polymerase-1,PARP-1)是一种丰富的ADP核糖基转移酶,可调节多种生物学过程。PARP-1被广泛认为是DNA损伤反应(DDR)中的一线反应分子。本文综述了PARP-1检测DNA损伤、DNA结合后PARP-1的激活和DNA断裂后PARP-1的释放的全过程。我们还讨论了PARP抑制剂(PARPi)结合后的变构后果以及调整其从DNA断裂释放的机会。现在有可能利用这种新的理解来设计新型PARPi,用于治疗由DNA上的PARP-1“捕获”引起的细胞毒性是所需的结果或完全适得其反的疾病。
Poly(ADP-ribosyl) polymerase-1(PARP-1) is an abundant ADP-ribosyl transferase that regulates various biological processes. PARP-1 is widely recognized as a first-line responder molecule in DNA damage response (DDR). Here, we review the full cycle of detecting the DNA damage by PARP-1, PARP-1 activation upon DNA binding, and PARP-1 release from DNA break. We also discuss the allosteric consequence upon binding of PARP inhibitors (PARPi) and the opportunity to tune its release from a DNA break. It is now possible to harness this new understanding to design novel PARPi for treating diseases where cell toxicity caused by PARP-1 “trapping” on DNA is either the desired consequence or entirely counterproductive.
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期刊: Molecular cell
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