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Publication : Micronuclei in Kif18a mutant mice form stable micronuclear envelopes and do not promote tumorigenesis.

First Author  Sepaniac LA Year  2021
Journal  J Cell Biol Volume  220
Issue  11 PubMed ID  34515734
Mgi Jnum  J:324223 Mgi Id  MGI:7276065
Doi  10.1083/jcb.202101165 Citation  Sepaniac LA, et al. (2021) Micronuclei in Kif18a mutant mice form stable micronuclear envelopes and do not promote tumorigenesis. J Cell Biol 220(11):e202101165
abstractText  Micronuclei, whole or fragmented chromosomes spatially separated from the main nucleus, are associated with genomic instability and have been identified as drivers of tumorigenesis. Paradoxically, Kif18a mutant mice produce micronuclei due to asynchronous segregation of unaligned chromosomes in vivo but do not develop spontaneous tumors. We report here that micronuclei in Kif18a mutant mice form stable nuclear envelopes. Challenging Kif18a mutant mice via deletion of the Trp53 gene led to formation of thymic lymphoma with elevated levels of micronuclei. However, loss of Kif18a had modest or no effect on survival of Trp53 homozygotes and heterozygotes, respectively. Micronuclei in cultured KIF18A KO cells form stable nuclear envelopes characterized by increased recruitment of nuclear envelope components and successful expansion of decondensing chromatin compared with those induced by nocodazole washout or radiation. Lagging chromosomes were also positioned closer to the main chromatin masses in KIF18A KO cells. These data suggest that not all micronuclei actively promote tumorigenesis.
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