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Updated: Jun 15, 2026
09:49
Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability
Published on: April 2, 2015
hMSH5 is a nucleocytoplasmic shuttling protein whose stability depends on its subcellular localization
François Lahaye1, Françoise Lespinasse, Pascal Staccini
1FRE 3086 Instabilité génétique: Maladies rares et cancers, Université de Nice Sophia-Antipolis, CNRS, Nice Cedex 2, France.
Nucleic Acids Research
|February 27, 2010
Summary
The human MSH5 protein (hMSH5) shuttles between the nucleus and cytoplasm, influencing genomic stability. Its nuclear presence is regulated by degradation and interaction with hMSH4, controlling DNA repair functions.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The MutS-homologous protein MSH5 is crucial for meiotic DNA recombination.
- Emerging evidence implicates human MSH5 (hMSH5) in mitotic recombination and DNA damage response, highlighting its role in genomic stability.
- Understanding hMSH5 regulation is key to comprehending its impact on genomic integrity.
Purpose of the Study:
- To investigate the intracellular trafficking and regulatory mechanisms of human MSH5 (hMSH5).
- To elucidate how hMSH5 localization and stability are controlled within the cell.
- To explore the potential role of hMSH4 in modulating hMSH5 nuclear retention.
Main Methods:
- Confocal microscopy was used to analyze the localization of wild-type and mutated hMSH5.
- Investigation of CRM1-dependent nuclear export signal (NES) and nuclear localization signal (NLS) activity.
- Assessment of hMSH5 stability in different subcellular compartments.
Main Results:
- hMSH5 exhibits nucleocytoplasmic shuttling, mediated by a CRM1-dependent NES and an NLS.
- hMSH5 stability is compartmentalized, with lower stability observed in the nucleus compared to the cytoplasm.
- Nuclear hMSH5 levels appear to be controlled by proteasomal degradation and potentially by hMSH4-mediated masking of the NES.
Conclusions:
- Nucleocytoplasmic shuttling and nuclear proteasomal degradation are key regulatory mechanisms for hMSH5 activity and nuclear content.
- These processes contribute to maintaining genomic stability by controlling nuclear hMSH5 levels.
- hMSH4 may retain hMSH5 in the nucleus by inhibiting its nuclear export, suggesting a cooperative role in DNA repair pathways.
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