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bioRxiv · 10.1101/2023.08.27.555027

The proteomic landscape of genotoxic stress-induced micronuclei

MacDonald, K. M.·Khan, S.·Kislinger, T. M.·Harding, S. M.
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Abstract

Micronuclei (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.

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MacDonald, K. M., Khan, S., Kislinger, T. M., Harding, S. M.. 2023-08-27. The proteomic landscape of genotoxic stress-induced micronuclei. https://doi.org/10.1101/2023.08.27.555027

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