聚ADP核糖聚合酶
DNA损伤
DNA
DNA修复
化学
细胞生物学
变构调节
分子生物学
生物
聚合酶
PARP抑制剂
计算生物学
遗传学
生物化学
酶
作者
Nootan Pandey,Ben E. Black
标识
DOI:10.1016/j.tibs.2021.01.014
摘要
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.
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