RT Journal Article
SR Electronic
T1 Chromosome length and gene density contribute to micronuclear membrane stability
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101210
DO 10.26508/lsa.202101210
VO 5
IS 2
A1 Anna E Mammel
A1 Heather Z Huang
A1 Amanda L Gunn
A1 Emma Choo
A1 Emily M Hatch
YR 2022
UL https://www.life-science-alliance.org/content/5/2/e202101210.abstract
AB Micronuclei are derived from missegregated chromosomes and frequently lose membrane integrity, leading to DNA damage, innate immune activation, and metastatic signaling. Here, we demonstrate that two characteristics of the trapped chromosome, length and gene density, are key contributors to micronuclei membrane stability and determine the timing of micronucleus rupture. We demonstrate that these results are not due to chromosome-specific differences in spindle position or initial protein recruitment during post-mitotic nuclear envelope assembly. Micronucleus size strongly correlates with lamin B1 levels and nuclear pore density in intact micronuclei, but, unexpectedly, lamin B1 levels do not completely predict nuclear lamina organization or membrane stability. Instead, small gene-dense micronuclei have decreased nuclear lamina gaps compared to large micronuclei, despite very low levels of lamin B1. Our data strongly suggest that nuclear envelope composition defects previously correlated with membrane rupture only partly explain membrane stability in micronuclei. We propose that an unknown factor linked to gene density has a separate function that inhibits the appearance of nuclear lamina gaps and delays membrane rupture until late in the cell cycle.