PCNA泛素化修饰对DNA损伤应答途径的调控

Role of PCNA Ubiquitination in Regulation of DNA Damage Response Pathways

机体细胞在多种化学物质和内外环境不断攻击下会诱发DNA损伤。为了维持基因组的稳定性,细胞内拥有一系列完善而精确的细胞应答机制来保护基因组DNA的完整性。细胞首先通过DNA损伤检测点,然后通过一系列细胞信号转导通路,启动细胞周期阻滞,进而介导细胞修复或凋亡。大量研究表明泛素化作为一种重要的蛋白质翻译后修饰方式,参与调控了多种细胞生理过程。近期研究表明,DNA损伤导致复制应激可诱发PCNA的翻译后泛素化修饰,泛素化修饰的PCNA可能参与了多种DNA损伤应激过程,影响细胞选择不同的DNA损伤应答途径,导致细胞截然不同的转归。因此,更好地了解PCNA泛素化的作用及其影响DNA损伤应答通路可为我们更深入地了解人类细胞如何调控异常的DNA代谢过程和癌症的发生和发展机制提供依据。

Eukaryotic cells possess a series of mechanisms to protect the integrity of genomic DNA. These include cellular signals transduction, cell cycle arrest, DNA repair or apoptosis pathways. A large number of studies have shown that post-translational modi？cations of PCNA involved in the regulation of a variety of physiological processes of protein. Recent studies have shown that DNA damage leads to replication stress can induce PCNA ubiquitination and sumoylation may be involved in a variety of DNA damage response pathways, identified to affect the cells selecting different DNA damage response pathways, leading to completely different outcomes. Therefore, better understanding the role of modified PCNA by SUMO and ubiquitin and its implications for DNA damage response can give us a deeper understanding of how human cells regulate aberrant DNA metabolism events and cancer initiation and development.