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PARP1、PARP2 和 PARP3 对核小体 DNA 碱基切除修复的影响。

Impact of PARP1, PARP2 & PARP3 on the Base Excision Repair of Nucleosomal DNA.

机构信息

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences (ICBFM SB RAS), Novosibirsk, Russia.

Novosibirsk State University, Novosibirsk, Russia.

出版信息

Adv Exp Med Biol. 2020;1241:47-57. doi: 10.1007/978-3-030-41283-8_4.

Abstract

DNA is constantly attacked by different damaging agents; therefore, it requires frequent repair. On the one hand, the base excision repair (BER) system is responsible for the repair of the most frequent DNA lesions. On the other hand, the formation of poly(ADP-ribose) is one of the main DNA damage response reactions that is catalysed by members of the PARP family. PARP1, which belongs to the PARP family and performs approximately 90% of PAR synthesis in cells, could be considered a main regulator of the BER process. Most of the experimental data concerning BER investigation have been obtained using naked DNA. However, in the context of the eukaryotic cell, DNA is compacted in the nucleus, and the lowest compaction level is represented by the nucleosome. Thus, the organization of DNA into the nucleosome impacts the DNA-protein interactions that are involved in BER processes. Poly(ADP-ribosyl)ation (PARylation) is thought to regulate the initiation of the BER process at the chromatin level. In this review, we focus on the mechanisms involved in BER in the nucleosomal context and the potential effect of PARylation, which is catalysed by DNA-dependent PARP1, PARP2 and PARP3 proteins, on this process.

摘要

DNA 经常受到不同损伤剂的攻击;因此,它需要频繁修复。一方面,碱基切除修复 (BER) 系统负责修复最常见的 DNA 损伤。另一方面,聚(ADP-核糖)的形成是 DNA 损伤反应的主要反应之一,由 PARP 家族成员催化。PARP1 属于 PARP 家族,在细胞中进行约 90%的 PAR 合成,可以被认为是 BER 过程的主要调节剂。大多数关于 BER 研究的实验数据都是使用裸露 DNA 获得的。然而,在真核细胞的背景下,DNA 被压缩在核内,最低的压缩水平由核小体代表。因此,DNA 组装成核小体影响参与 BER 过程的 DNA-蛋白质相互作用。聚(ADP-核糖)化 (PARylation) 被认为在染色质水平上调节 BER 过程的起始。在这篇综述中,我们重点关注核小体背景下 BER 涉及的机制以及由 DNA 依赖性 PARP1、PARP2 和 PARP3 蛋白催化的 PARylation 对该过程的潜在影响。

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