Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Oncode Institute, Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
J Cell Sci. 2018 Jul 9;131(13):jcs214742. doi: 10.1242/jcs.214742.
DNA in micronuclei is likely to get damaged. When shattered DNA from micronuclei gets reincorporated into the primary nucleus, aberrant rearrangements can take place, a phenomenon referred to as chromothripsis. Here, we investigated how chromatids from micronuclei act in subsequent divisions and how this affects their fate. We observed that the majority of chromatids derived from micronuclei fail to establish a proper kinetochore in mitosis, which is associated with problems in chromosome alignment, segregation and spindle assembly checkpoint activation. Remarkably, we found that, upon their formation, micronuclei already display decreased levels of important kinetochore assembly factors. Importantly, these defects favour the exclusion of the micronucleus over the reintegration into the primary nucleus over several divisions. Interestingly, the defects observed in micronuclei are likely overcome once micronuclei are reincorporated into the primary nuclei, as they further propagate normally. We conclude that the formation of a separate small nuclear entity represents a mechanism for the cell to delay the stable propagation of excess chromosome(s) and/or damaged DNA, by inducing kinetochore defects.
微核中的 DNA 很可能会受损。当来自微核的破碎 DNA 重新整合到主核中时，可能会发生异常重排，这种现象被称为染色体重排。在这里，我们研究了微核中的染色质在随后的分裂中是如何作用的，以及这如何影响它们的命运。我们观察到，大多数来自微核的染色质在有丝分裂中未能建立适当的动粒，这与染色体排列、分离和纺锤体组装检查点激活的问题有关。值得注意的是，我们发现，微核形成时，已经显示出重要的动粒组装因子水平降低。重要的是，这些缺陷有利于微核在多次分裂中被排除在外，而不是重新整合到主核中。有趣的是，一旦微核重新整合到主核中，微核中观察到的缺陷就可能被克服，因为它们会进一步正常传播。我们得出结论，形成一个单独的小核实体是细胞通过诱导动粒缺陷来延迟多余染色体和/或受损 DNA 的稳定传播的一种机制。
