Chromosome fusion is a frequent intermediate in oncogenic chromosome rearrangements and has been proposed to cause multiple tumor-driving abnormalities. In conventional experimental systems, however, these abnormalities were often induced by randomly induced chromosome fusions involving multiple different chromosomes. It was therefore not well understood whether a single defined type of chromosome fusion, which is reminiscent of a sporadic fusion in tumor cells, has the potential to cause chromosome instabilities. Here, we developed a human cell-based sister chromatid fusion visualization system (FuVis), in which a single defined sister chromatid fusion is induced by CRISPR/Cas9 concomitantly with mCitrine expression. The fused chromosome subsequently developed extra-acentric chromosomes, including chromosome scattering, indicative of chromothripsis. Live-cell imaging and statistical modeling indicated that sister chromatid fusion generated micronuclei (MN) in the first few cell cycles and that cells with MN tend to display cell cycle abnormalities. The powerful FuVis system thus demonstrates that even a single sporadic sister chromatid fusion can induce chromosome instability and destabilize the cell cycle through MN formation.

中文翻译：

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由单一确定的姐妹染色单体融合引起的染色体不稳定。


染色体融合是致癌染色体重排中常见的中间体，并被认为会导致多种肿瘤驱动异常。然而，在传统的实验系统中，这些异常通常是由涉及多个不同染色体的随机诱导的染色体融合引起的。因此，尚不清楚单一定义类型的染色体融合（让人想起肿瘤细胞中的零星融合）是否有可能导致染色体不稳定。在这里，我们开发了一种基于人类细胞的姐妹染色单体融合可视化系统（FuVis），其中通过 CRISPR/Cas9 诱导单一定义的姐妹染色单体融合，同时表达 mCitrine。融合的染色体随后发育出额外的无着丝粒染色体，包括染色体分散，表明染色体碎裂。活细胞成像和统计模型表明，姐妹染色单体融合在最初的几个细胞周期中产生微核（MN），并且具有 MN 的细胞往往表现出细胞周期异常。因此，强大的 FuVis 系统表明，即使是单个零星的姐妹染色单体融合也可能导致染色体不稳定，并通过 MN 形成破坏细胞周期的稳定性。