Zilio Nicola, Eifler-Olivi Karolin, Ulrich Helle D
Institute of Molecular Biology (IMB), Ackermannweg 4, D-55128, Mainz, Germany.
Adv Exp Med Biol. 2017;963:51-87. doi: 10.1007/978-3-319-50044-7_4.
Like in most other areas of cellular metabolism, the functions of the ubiquitin-like modifier SUMO in the maintenance of genome stability are manifold and varied. Perturbations of global sumoylation causes a wide spectrum of phenotypes associated with defects in DNA maintenance, such as hypersensitivity to DNA-damaging agents, gross chromosomal rearrangements and loss of entire chromosomes. Consistent with these observations, many key factors involved in various DNA repair pathways have been identified as SUMO substrates. However, establishing a functional connection between a given SUMO target, the cognate SUMO ligase and a relevant phenotype has remained a challenge, mainly because of the difficulties involved in identifying important modification sites and downstream effectors that specifically recognize the target in its sumoylated state. This review will give an overview over the major pathways of DNA repair and genome maintenance influenced by the SUMO system and discuss selected examples of SUMO's actions in these pathways where the biological consequences of the modification have been elucidated.
与细胞代谢的大多数其他领域一样,类泛素修饰因子SUMO在维持基因组稳定性方面的功能是多方面且多样的。整体SUMO化的扰动会导致一系列与DNA维持缺陷相关的表型,如对DNA损伤剂的超敏反应、大规模染色体重排以及整条染色体的丢失。与这些观察结果一致,许多参与各种DNA修复途径的关键因子已被确定为SUMO底物。然而,在给定的SUMO靶标、同源SUMO连接酶和相关表型之间建立功能联系仍然是一项挑战,主要是因为难以确定重要的修饰位点和在其SUMO化状态下特异性识别靶标的下游效应物。本综述将概述受SUMO系统影响的DNA修复和基因组维持的主要途径,并讨论SUMO在这些途径中的作用的选定实例,其中修饰的生物学后果已经阐明。