聚腺苷二磷酸核糖基化在 DNA 损伤反应和癌症治疗中的作用。
Poly-ADP ribosylation in DNA damage response and cancer therapy.
机构信息
Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California, USA.
Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA.
出版信息
Mutat Res Rev Mutat Res. 2019 Apr-Jun;780:82-91. doi: 10.1016/j.mrrev.2017.09.004. Epub 2017 Sep 20.
Abstract
Poly(ADP-ribosyl)ation (aka PARylation) is a unique protein post-translational modification (PTM) first described over 50 years ago. PARylation regulates a number of biological processes including chromatin remodeling, the DNA damage response (DDR), transcription, apoptosis, and mitosis. The subsequent discovery of poly(ADP-ribose) polymerase-1 (PARP-1) catalyzing DNA-dependent PARylation spearheaded the field of DDR. The expanding knowledge about the poly ADP-ribose (PAR) recognition domains prompted the discovery of novel DDR factors and revealed crosstalk with other protein PTMs including phosphorylation, ubiquitination, methylation and acetylation. In this review, we highlight the current knowledge on PAR-regulated DDR, PAR recognition domain, and PARP inhibition in cancer therapy.
摘要
聚（ADP-核糖）化（又名 PAR 化）是一种独特的蛋白质翻译后修饰（PTM），最早在 50 多年前被描述。PAR 化调节多种生物过程，包括染色质重塑、DNA 损伤反应（DDR）、转录、细胞凋亡和有丝分裂。随后发现聚（ADP-核糖）聚合酶-1（PARP-1）催化 DNA 依赖性 PAR 化，开创了 DDR 领域。对聚 ADP-核糖（PAR）识别结构域的不断深入的了解促使发现了新的 DDR 因子，并揭示了与其他蛋白质 PTM（包括磷酸化、泛素化、甲基化和乙酰化）的交叉对话。在这篇综述中，我们重点介绍了目前关于 PAR 调节的 DDR、PAR 识别结构域以及 PARP 抑制在癌症治疗中的知识。
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