Abstract
SUMMARYMicronuclei (MN) are induced by various genotoxic stressors and amass nuclear- and cytoplasmic-resident proteins, priming the cell for MN-driven signalling cascades. Here, we measure the proteome of micronuclear, cytoplasmic, and nuclear fractions from human cells exposed to a panel of six genotoxins, comprehensively profiling their MN protein landscape. We find that MN assemble a proteome distinct from both surrounding cytoplasm and parental nuclei, with a core composition that is independent of the specific inciting stressor. Across stress conditions, MN are significantly depleted for spliceosome machinery and replication stress response proteins, but are enriched for a subset of the replisome. We find that the loss of splicing machinery within transcriptionally active MN contributes to intra-MN DNA damage, a known precursor to chromothripsis. This dataset represents a unique resource detailing the proteomic landscape of MN, guiding mechanistic studies of MN generation and MN-associated outcomes of genotoxic stress.
Publisher
Cold Spring Harbor Laboratory
Reference39 articles.
1. Catastrophic Nuclear Envelope Collapse in Cancer Cell Micronuclei
2. Nuclear envelope assembly defects link mitotic errors to chromothripsis
3. MacDonald KM , Nicholson-puthenveedu S , Tageldein MM , Khasnis S , Arrowsmith CH , Harding SM . Nat Commun. 2023;1–15.
4. Abdisalaam S , Mukherjee S , Bhattacharya S , Kumari S , Sinha D , Ortega J , et al. Nucleic Acids Res. 2022;1–19.
5. Mitotic progression following DNA damage enables pattern recognition within micronuclei