Biology of Centrosomes and Genetic Instability Lab, Institut Curie, PSL Research University, CNRS UMR144, 12 rue Lhomond, Paris, 75005, France.
Bioessays. 2020 Oct;42(10):e2000105. doi: 10.1002/bies.202000105. Epub 2020 Sep 3.
Polyploid cells contain multiple copies of all chromosomes. Polyploidization can be developmentally programmed to sustain tissue barrier function or to increase metabolic potential and cell size. Programmed polyploidy is normally associated with terminal differentiation and poor proliferation capacity. Conversely, non-programmed polyploidy can give rise to cells that retain the ability to proliferate. This can fuel rapid genome rearrangements and lead to diseases like cancer. Here, the mechanisms that generate polyploidy are reviewed and the possible challenges upon polyploid cell division are discussed. The discussion is framed around a recent study showing that asynchronous cell cycle progression (an event that is named "chronocrisis") of different nuclei from a polyploid cell can generate DNA damage at mitotic entry. The potential mechanisms explaining how mitosis in non-programmed polyploid cells can generate abnormal karyotypes and genetic instability are highlighted.
多倍体细胞含有所有染色体的多个拷贝。多倍体化可以通过发育编程来维持组织屏障功能或增加代谢潜力和细胞大小。有计划的多倍体化通常与终末分化和增殖能力差有关。相反，非计划的多倍体化可以产生保留增殖能力的细胞。这可以促进快速的基因组重排，并导致癌症等疾病。在这里，我们回顾了产生多倍体的机制，并讨论了多倍体细胞分裂可能面临的挑战。讨论围绕着最近的一项研究展开，该研究表明，来自多倍体细胞的不同核的异步细胞周期进程（一个名为“chronocrisis”的事件）可以在有丝分裂进入时产生 DNA 损伤。强调了可以解释非计划多倍体细胞有丝分裂如何产生异常核型和遗传不稳定性的潜在机制。
