期刊
JOURNAL OF CELL SCIENCE
卷 131, 期 13, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.214742
关键词
Micronucleus; Chromosome segregation; Aneuploidy
类别
资金
- Marie Curie ITN Project PLOIDYNET [607722]
- KWF Kankerbestrijding (Dutch Cancer Foundation) [NKI-2015-7832]
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.
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