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Related Concept Videos

Nucleotide Excision Repair01:38

Nucleotide Excision Repair

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Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
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Regulation of Nuclear Protein Sorting01:45

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
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Cell Membrane Repair Assay Using a Two-photon Laser Microscope
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ESCRT machinery: Damage control at the nuclear membrane.

Leandro N Ventimiglia1, Juan Martin-Serrano1

  • 1Department of Infectious Diseases, King's College London, London SE1 9RT, UK.

Cell Research
|May 7, 2016
PubMed
Summary

Nuclear envelope (NE) ruptures during cell migration through confined spaces. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery is crucial for resealing these nuclear disruptions.

Area of Science:

  • Cell biology
  • Molecular and cell mechanics
  • Biophysics

Background:

  • The nuclear envelope (NE) is a vital barrier protecting cellular DNA.
  • NE rupture is generally considered rare in healthy cells during interphase.
  • Cellular migration, especially through restrictive environments, presents mechanical challenges.

Purpose of the Study:

  • To investigate the occurrence and mechanisms of nuclear envelope (NE) disruption during cell migration.
  • To identify the cellular machinery involved in repairing transient NE breaches.
  • To understand the implications of NE integrity for cell motility.

Main Methods:

  • Live-cell imaging of migrating cells in confined microenvironments.
  • High-resolution microscopy to visualize nuclear envelope dynamics.

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  • Genetic and pharmacological manipulation of the Endosomal Sorting Complex Required for Transport (ESCRT) pathway.

    • Main Results:

    • Transient ruptures in the nuclear envelope (NE) continuity were observed in cells migrating through confined spaces.
    • The Endosomal Sorting Complex Required for Transport (ESCRT) machinery was identified as essential for resealing these NE discontinuities.
    • ESCRT-dependent NE repair is critical for maintaining genomic integrity during cell migration.

    Conclusions:

    • Nuclear envelope (NE) rupture is a more frequent event during cell migration in confined spaces than previously thought.
    • The Endosomal Sorting Complex Required for Transport (ESCRT) plays a critical role in repairing NE breaches.
    • Understanding NE repair mechanisms is important for cell motility and preventing DNA damage.