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Rapid Detection and Signaling of DNA Damage by PARP-1
Trends in Biochemical Sciences ( IF 13.8 ) Pub Date : 2021-03-03 , DOI: 10.1016/j.tibs.2021.01.014
Nootan Pandey 1 , Ben E Black 1
Affiliation  

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 DNA damage by PARP-1, PARP-1 activation upon DNA binding, and PARP-1 release from a 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.



中文翻译:

PARP-1 对 DNA 损伤的快速检测和信号传导

Poly(ADP-ribosyl) polymerase-1 (PARP-1) 是一种丰富的 ADP-核糖基转移酶,可调节各种生物过程。PARP-1 被广泛认为是 DNA 损伤反应 (DDR) 中的一线反应分子。在这里,我们回顾了通过 PARP-1 检测 DNA 损伤、DNA 结合时 PARP-1 激活以及 DNA 断裂后 PARP-1 释放的完整周期。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 断裂中释放的机会。现在可以利用这种新的认识来设计新的 PARPi 来治疗由 PARP-1“捕获”在 DNA 上引起的细胞毒性是预期结果或完全适得其反的疾病。

更新日期:2021-03-03
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