Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.
Curr Issues Mol Biol. 2020;35:85-98. doi: 10.21775/cimb.035.085. Epub 2019 Aug 18.
Telomeres are a unique structure of DNA repeats covered by proteins at the ends of the chromosomes that protect the coding regions of the genome and function as a biological clock. They require a tight regulation of the factors covering and protecting their structure, as they are shortened with each cell division to limit the ability of cells to replicate uncontrollably. Additionally, they protect the chromosome ends from DNA damage responses and thereby, prevent genomic instability. Telomere dysfunction can lead to chromosomal abnormalities and cancer. Therefore, dysregulation of any of the factors that regulate the integrity of the telomeres will have implications to chromosomal stability, replicative lifespan and may lead to cell transformation. This review will cover the main factors participating in the normal function of the telomeres and how these are regulated by the ubiquitin and SUMO systems. Accumulating evidence indicate that the ubiquitin and SUMO pathways are significant regulators of the shelterin complex and other chromatin modifiers, which are important for telomere structure integrity. Furthermore, the crosstalk between these two pathways has been reported in telomeric DNA repair. A better understanding of the factors contributing to telomere biology, and how they are regulated, is important for the design of new strategies for cancer therapies and regenerative medicine.
端粒是一种独特的 DNA 重复结构，由染色体末端的蛋白质覆盖，可保护基因组的编码区，并充当生物钟。它们需要对覆盖和保护其结构的因素进行严格的调节，因为随着每个细胞分裂，它们会缩短，从而限制细胞不受控制地复制的能力。此外，它们还可以防止染色体末端发生 DNA 损伤反应，从而防止基因组不稳定。端粒功能障碍可导致染色体异常和癌症。因此，调节端粒完整性的任何因素的失调都会对染色体稳定性、复制寿命产生影响，并可能导致细胞转化。本综述将涵盖参与端粒正常功能的主要因素，以及泛素和 SUMO 系统如何对其进行调节。越来越多的证据表明，泛素和 SUMO 途径是保护套复合物和其他染色质修饰物的重要调节剂，这些对于端粒结构的完整性很重要。此外，这两种途径在端粒 DNA 修复中存在相互作用。更好地了解端粒生物学的贡献因素，以及它们是如何被调节的，对于设计癌症治疗和再生医学的新策略非常重要。
