RRC ID 81127
著者 Galanopoulou O, Tachmatzidi EC, Deligianni E, Botskaris D, Nikolaou KC, Gargani S, Dalezios Y, Chalepakis G, Talianidis I.
タイトル Endonucleosis mediates internalization of cytoplasm into the nucleus.
ジャーナル Nat Commun
Abstract Setd8 regulates transcription elongation, mitotic DNA condensation, DNA damage response and replication licensing. Here we show that, in mitogen-stimulated liver-specific Setd8-KO mice, most of the hepatocytes are eliminated by necrosis but a significant number of them survive via entering a stage exhibiting several senescence-related features. Setd8-deficient hepatocytes had enlarged nuclei, chromosomal hyperploidy and nuclear engulfments progressing to the formation of intranuclear vesicles surrounded by nuclear lamina. These vesicles contain glycogen, cytoplasmic proteins and even entire organelles. We term this process "endonucleosis". Intranuclear vesicles are absent in hepatocytes of Setd8/Atg5 knockout mice, suggesting that the process requires the function of the canonical autophagy machinery. Endonucleosis and hyperploidization are temporary, early events in the surviving Setd8-deficient cells. Larger vesicles break down into microvesicles over time and are eventually eliminated. The results reveal sequential events in cells with extensive DNA damage, which function as part of survival mechanisms to prevent necrotic death.
巻・号 15(1)
ページ 5843
公開日 2024-7-11
DOI 10.1038/s41467-024-50259-3
PII 10.1038/s41467-024-50259-3
PMID 38992049
PMC PMC11239883
MeSH Animals Autophagy / physiology Autophagy-Related Protein 5 / genetics Autophagy-Related Protein 5 / metabolism Cell Nucleus* / metabolism Cytoplasm* / metabolism DNA Damage Hepatocytes* / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout* Necrosis
IF 12.121
リソース情報
実験動物マウス RBRC00806