Institute of Molecular Medicine, Ulm University, Life Science Building N27, James Franck-Ring/Meyerhofstrasse, 89081, Ulm, Germany.
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.
Cell Mol Life Sci. 2018 Oct;75(20):3771-3779. doi: 10.1007/s00018-018-2891-z. Epub 2018 Jul 31.
Loss of chromosome integrity is a major contributor to cancer. Checkpoints within the cell division cycle that facilitate the accuracy and outcome of chromosome segregation are thus critical pathways for preserving chromosome integrity and preventing chromosomal instability. The spindle assembly checkpoint, the decatenation checkpoint and the post-mitotic tetraploidy checkpoint ensure the appropriate establishment of the spindle apparatus, block mitotic entry upon entanglement of chromosomes or prevent further progression of post-mitotic cells that display massive spindle defects. Most of our knowledge on these mechanisms originates from studies conducted in yeast, cancer cell lines and differentiated cells. Considering that in many instances cancer derives from transformed stem and progenitor cells, our knowledge on these checkpoints in these cells just started to emerge. With this review, we provide a general overview of the current knowledge of these checkpoints in embryonic as well as in adult stem and progenitor cells with a focus on the hematopoietic system and outline common mis-regulations of their function associated with cancer and leukemia. Most cancers are aging-associated diseases. We will thus also discuss changes in the function and outcome of these checkpoints upon aging of stem and progenitor cells.
染色体完整性的丧失是癌症的主要诱因之一。因此，细胞分裂周期内有助于染色体分离准确性和结果的检查点是维持染色体完整性和防止染色体不稳定性的关键途径。纺锤体组装检查点、解连环检查点和有丝分裂后四倍体检查点确保了纺锤体装置的适当建立，在染色体缠绕时阻止有丝分裂进入，并防止在显示大量纺锤体缺陷的有丝分裂后细胞进一步进展。我们对这些机制的大部分了解来自于在酵母、癌细胞系和分化细胞中进行的研究。考虑到在许多情况下，癌症来源于转化的干细胞和祖细胞，我们对这些细胞中这些检查点的了解才刚刚开始出现。通过这篇综述，我们提供了胚胎以及成体干细胞中这些检查点的当前知识的概述，重点是造血系统，并概述了与癌症和白血病相关的其功能常见的失调。大多数癌症是与衰老相关的疾病。因此，我们还将讨论随着干细胞和祖细胞的衰老，这些检查点的功能和结果的变化。
