Dantuma Nico P, van Attikum Haico
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
EMBO J. 2016 Jan 4;35(1):6-23. doi: 10.15252/embj.201592595. Epub 2015 Dec 1.
A timely and accurate cellular response to DNA damage requires tight regulation of the action of DNA damage response (DDR) proteins at lesions. A multitude of posttranslational modifications (PTMs) of chromatin and chromatin-associated proteins coordinates the recruitment of critical proteins that dictate the appropriate DNA repair pathway and enable the actual repair of lesions. Phosphorylation, ubiquitylation, SUMOylation, neddylation, poly(ADP-ribosyl)ation, acetylation, and methylation are among the DNA damage-induced PTMs that have taken center stage as important DDR regulators. Redundant and multivalent interactions of DDR proteins with PTMs may not only be a means to facilitate efficient relocalization, but also a feature that allows high temporal and spatial resolution of protein recruitment to, and extraction from, DNA damage sites. In this review, we will focus on the complex interplay between such PTMs, and discuss the importance of their interconnectivity in coding DNA lesions and maintaining the integrity of the genome.
细胞对DNA损伤做出及时准确的反应需要对DNA损伤反应（DDR）蛋白在损伤位点的作用进行严格调控。染色质及与染色质相关蛋白的多种翻译后修饰（PTM）协调关键蛋白的招募，这些关键蛋白决定了适当的DNA修复途径，并实现损伤的实际修复。磷酸化、泛素化、SUMO化、NEDD化、聚（ADP-核糖）化、乙酰化和甲基化是DNA损伤诱导的PTM，它们已成为重要的DDR调节因子并占据核心地位。DDR蛋白与PTM之间的冗余和多价相互作用不仅可能是促进有效重新定位的一种方式，也是一种能够在高时间和空间分辨率下将蛋白质招募到DNA损伤位点并从该位点提取的特性。在本综述中，我们将重点关注此类PTM之间的复杂相互作用，并讨论它们的相互连接在编码DNA损伤和维持基因组完整性方面的重要性。
