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  • New Compartment in Mammalian Cells Offers Fresh Perspective on DNA Management

    In an exciting new development in cell biology, scientists at ETH Zurich have identified a new compartment within mammalian cells, termed the "exclusome." This compartment, detailed in the journal Molecular Biology of the Cell, comprises DNA rings, or plasmids.

    Historically, eukaryotic cells (those with nuclei) have been understood to house most of their DNA within the cell nucleus, systematically arranged into chromosomes. However, this discovery challenges that notion. It appears that the cell nucleus actively removes certain DNA rings, either those originating externally or ones, termed telomeric rings, that form from the chromosome's capped ends, particularly in certain cancer cells. These DNA rings, unlike regular chromosomes, do not hold the templates for proteins.

    ETH researchers demonstrated that these ejected DNA rings, along with externally originating plasmids, find a place in the cell plasma. Ruth Kroschewski, from the Institute of Biochemistry at ETH Zurich, mentioned, “It’s one of the key hygiene functions cells perform to protect the chromosomes. Plasmids that can’t be separated off could theoretically embed themselves in the chromosomes. More likely is that the nuclear plasmid genes of viruses or bacteria are translated into proteins, which disrupts the cell physiology.”

    The broader functions of the exclusome remain a topic of inquiry. Kroschewski's team postulates its potential involvement in cellular immunological memory. Existing studies have shown certain proteins binding to DNA in cell plasma, possibly inciting a chain reaction leading to the production of inflammatory messengers. If these proteins attach to the DNA rings within the exclusome, it could result in continuous inflammatory signals, possibly instigating autoimmune responses.

    The origins of the exclusome might be traced back to the dawn of eukaryotic evolution. This compartment's envelope, though reminiscent of the cell nucleus, exhibits distinct features. As Kroschewski elucidated, the exclusome envelope possesses gaps typically seen in the nuclear envelope only during its nascent stages. As time progresses, these gaps either seal up or get occupied by specific proteins in the nuclear envelope, a process not evident in the exclusome.

    The criteria determining which DNA ends up in this incomplete membrane, as opposed to the fully formed nuclear envelope, remains uncertain. Kroschewski speculates that only chromosomal DNA receives the privilege of a complete nuclear casing, while other forms, like extrachromosomal DNA, do not qualify. The exact qualifications, however, are yet to be discerned.

    Kroschewski and her team are setting their sights on a deeper understanding of the exclusome, keenly interested in the unique cellular adjustments concerning plasmid DNA and the criteria guiding plasmid deposits within the exclusome.

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