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

Document Type

Article

Publication Date

11-1-2021

Publication Title

The Journal of cell biology

Keywords

JMG

JAX Source

J Cell Biol 2021 Nov; 220(11):e202101165

Volume

220

Issue

11

ISSN

1540-8140

PMID

34515734

DOI

https://doi.org/10.1083/jcb.202101165

Grant

CA034196

Abstract

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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