Kassab Muzaffer Ahmad, Yu Lily L, Yu Xiaochun
1Department of Cancer Genetics & Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA 91010 USA.
Westridge School, 324 Madeline Dr., Pasadena, CA 91105 USA.
Cell Biosci. 2020 Jan 29;10:7. doi: 10.1186/s13578-020-0375-y. eCollection 2020.
Poly(ADP-ribosyl)ation (PARylation) mediated by poly ADP-ribose polymerases (PARPs) plays a key role in DNA damage repair. Suppression of PARylation by PARP inhibitors impairs DNA damage repair and induces apoptosis of tumor cells with repair defects. Thus, PARP inhibitors have been approved by the US FDA for various types of cancer treatment. However, recent studies suggest that dePARylation also plays a key role in DNA damage repair. Instead of antagonizing PARylation, dePARylation acts as a downstream step of PARylation in DNA damage repair. Moreover, several types of dePARylation inhibitors have been developed and examined in the preclinical studies for cancer treatment. In this review, we will discuss the recent progress on the role of dePARylation in DNA damage repair and cancer suppression. We expect that targeting dePARylation could be a promising approach for cancer chemotherapy in the future.
由聚腺苷酸核糖聚合酶（PARP）介导的聚（ADP - 核糖）化（PARylation）在DNA损伤修复中起关键作用。PARP抑制剂对PARylation的抑制会损害DNA损伤修复，并诱导具有修复缺陷的肿瘤细胞凋亡。因此，PARP抑制剂已被美国食品药品监督管理局（FDA）批准用于多种类型的癌症治疗。然而，最近的研究表明，去聚（ADP - 核糖）化（dePARylation）在DNA损伤修复中也起关键作用。dePARylation并非拮抗PARylation，而是在DNA损伤修复中作为PARylation的下游步骤发挥作用。此外，已经开发了几种类型的去聚（ADP - 核糖）化抑制剂，并在癌症治疗的临床前研究中进行了检测。在本综述中，我们将讨论dePARylation在DNA损伤修复和癌症抑制作用方面的最新进展。我们期望靶向dePARylation在未来可能成为一种有前景的癌症化疗方法。
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