Bhachoo Jai S, Garvin Alexander J
SUMO Biology Lab, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire LS2 9JT, U.K.
Biochem Soc Trans. 2024 Apr 24;52(2):773-792. doi: 10.1042/BST20230862.
The preservation of genome integrity requires specialised DNA damage repair (DDR) signalling pathways to respond to each type of DNA damage. A key feature of DDR is the integration of numerous post-translational modification signals with DNA repair factors. These modifications influence DDR factor recruitment to damaged DNA, activity, protein-protein interactions, and ultimately eviction to enable access for subsequent repair factors or termination of DDR signalling. SUMO1-3 (small ubiquitin-like modifier 1-3) conjugation has gained much recent attention. The SUMO-modified proteome is enriched with DNA repair factors. Here we provide a snapshot of our current understanding of how SUMO signalling impacts the major DNA repair pathways in mammalian cells. We highlight repeating themes of SUMO signalling used throughout DNA repair pathways including the assembly of protein complexes, competition with ubiquitin to promote DDR factor stability and ubiquitin-dependent degradation or extraction of SUMOylated DDR factors. As SUMO 'addiction' in cancer cells is protective to genomic integrity, targeting components of the SUMO machinery to potentiate DNA damaging therapy or exacerbate existing DNA repair defects is a promising area of study.
基因组完整性的维持需要专门的DNA损伤修复（DDR）信号通路来应对每种类型的DNA损伤。DDR的一个关键特征是众多翻译后修饰信号与DNA修复因子的整合。这些修饰影响DDR因子募集到受损DNA、活性、蛋白质-蛋白质相互作用，并最终使其移除，以便后续修复因子能够接入或终止DDR信号。SUMO1-3（小泛素样修饰物1-3）缀合最近受到了很多关注。SUMO修饰的蛋白质组富含DNA修复因子。在这里，我们简要介绍一下我们目前对SUMO信号如何影响哺乳动物细胞中主要DNA修复途径的理解。我们强调了在整个DNA修复途径中使用的SUMO信号的重复主题，包括蛋白质复合物的组装、与泛素竞争以促进DDR因子稳定性以及泛素依赖性降解或提取SUMO化的DDR因子。由于癌细胞中的SUMO“成瘾”对基因组完整性具有保护作用，靶向SUMO机制的成分以增强DNA损伤治疗或加剧现有的DNA修复缺陷是一个有前景的研究领域。
