Ulrich Helle D, Takahashi Diane T
Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms EN6 3LD, UK.
Chromosoma. 2013 Aug;122(4):259-74. doi: 10.1007/s00412-013-0410-4. Epub 2013 Apr 12.
The eukaryotic sliding clamp, proliferating cell nuclear antigen (PCNA), acts as a central coordinator of DNA transactions by providing a multivalent interaction surface for factors involved in DNA replication, repair, chromatin dynamics and cell cycle regulation. Posttranslational modifications (PTMs), such as mono- and polyubiquitylation, sumoylation, phosphorylation and acetylation, further expand the repertoire of PCNA's binding partners. These modifications affect PCNA's activity in the bypass of lesions during DNA replication, the regulation of alternative damage processing pathways such as homologous recombination and DNA interstrand cross-link repair, or impact on the stability of PCNA itself. In this review, we summarise our current knowledge about how the PTMs are "read" by downstream effector proteins that mediate the appropriate action. Given the variety of interaction partners responding to PCNA's modified forms, the ensemble of PCNA modifications serves as an instructive model for the study of biological signalling through PTMs in general.
真核生物滑动夹增殖细胞核抗原(PCNA)通过为参与DNA复制、修复、染色质动力学和细胞周期调控的因子提供多价相互作用表面,充当DNA事务的中央协调者。翻译后修饰(PTM),如单泛素化和多泛素化、SUMO化、磷酸化和乙酰化,进一步扩展了PCNA结合伙伴的范围。这些修饰影响PCNA在DNA复制过程中绕过损伤的活性、对同源重组和DNA链间交联修复等替代损伤处理途径的调控,或对PCNA自身稳定性的影响。在本综述中,我们总结了目前关于下游效应蛋白如何“读取”PTM以介导适当作用的知识。鉴于对PCNA修饰形式作出反应的相互作用伙伴种类繁多,PCNA修饰的整体作用通常为通过PTM进行生物信号研究提供了一个指导性模型。