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Published on: April 16, 2021
Spatial Cross-Talk between Oxidative Stress and DNA Replication in Human Fibroblasts
Marko Radulovic1,2, Noor O Baqader1, Kai Stoeber3
1Division of Medicine, University College London, Center for Nephrology , Royal Free Campus, Rowland Hill Street, London NW3 2PF, United Kingdom.
Cellular protein distribution shifts between nucleus and cytoplasm during DNA replication stress or oxidative damage. Understanding these dynamic spatial changes is crucial for cell function and disease insights.
Area of Science:
- Proteomics
- Cell Biology
- Systems Biology
Background:
- Cellular responses involve complex protein trafficking and abundance changes.
- Nuclear-cytoplasmic protein distribution is critical for cellular function.
Purpose of the Study:
- To analyze differential protein distribution between nucleus and cytoplasm under cell-cycle arrest and oxidative stress.
- To identify proteins involved in cross-talk between DNA replication and oxidative stress responses.
Main Methods:
- Mass spectrometry-based proteomics.
- Differential network analysis of protein localization.
- Quantitative analysis of spatial protein redistribution.
Main Results:
- Identified 401 proteins with significant changes in subcellular distribution.
- Found 49 proteins strongly affected by both DNA replication stress and oxidative stress.
- Detailed dynamic spatial distribution for various cellular processes including signaling pathways, protein complexes, and transport machinery.
Conclusions:
- Cross-compartmental communication is integral to the system biology of spatially heterogeneous cells.
- Coordinated spatial redistribution of protein networks underlies functional changes and cellular responses.
- Dynamic spatial protein data are essential for a comprehensive understanding of cellular function and disease mechanisms, particularly in cancer.
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