Meet the ‘exclusome’: A mini-organ just discovered in cells that defends the genome from attack
A newfound mini-organ in mammal cells is a trap that snaps shut around tiny rings of DNA. Scientists believe it may be an in-built defense system for the genome and a relic from a time before complex cells.
All animals, plants and fungi are eukaryotic, meaning their cells house their DNA within a special compartment called the nucleus. But some of the cell’s DNA exists outside this structure, in the fluid-filled body of the cell called the cytoplasm. In addition, foreign genetic material from viruses and bacteria can get injected into the cytoplasm.
Scientists don’t fully understand how these free-floating bits of genetic material are kept away from the nucleus, or why they quickly degrade if the blueprints in that material aren’t used to make proteins.
But in a recent study, researchers identified a unique structure that could help explain how cells might keep this DNA away from the nucleus.
The never-before-seen structure, which the researchers dubbed an “exclusome,” encloses this DNA. The researchers speculate that the process that this possible new organelle, or specialized cellular compartment, uses to catch DNA could be related to how the nucleus developed in early eukaryotic cells.
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The findings could shed light on how cells respond to invaders and on the development of cancer and autoimmune conditions, the researchers said.
“If DNA enters a human cell, then the cell has a … defense system,” which means that “the DNA is caught in the cytoplasm,” said senior study author Ruth Kroschewski, a group leader at the Institute of Biochemistry at ETH Zurich in Switzerland, which was published in September in the journal Molecular Biology of the Cell.
Kroschewski and her colleagues introduced teensy loops of DNA called plasmids into different types of human cells, including cells grown from donated tissue and HeLa cells — the first “immortal” cell line derived from the cancer cells of a woman named Henrietta Lacks. They found that, in every case, a double membrane formed around the plasmid, forming the structure they call an exclusome.
Inside the structure, they also found genetic material that codes for telomeres, the “caps” at the end of chromosomes that protect DNA from becoming destroyed. This telomere DNA can get pinched off into rings that float around the cell.
Like the nucleus, the exclusome has a double membrane and some of the same proteins. But it lacks other elements, such as nuclear pore complexes — structures that let only select molecules into the nucleus. The researchers also found that exclusomes stayed in the cell through several rounds of cell division, but they didn’t end up in the new cells made in that process.
The process of capturing plasmids could be an evolutionary relic of the cellular machinery that helped form the first nuclear membranes around chromosomal DNA, Kroschewski said. But exclusomes seem unique in that they only capture genetic material that the cell thinks is potentially dangerous or unnecessary.
Exclusomes may also play a role in autoimmune disease, Kroschewski said. If a pathogen’s DNA remains in the cell long after the invader injected it, this might tell cells that there is still an infection that needs fighting.
Birgitte Regenberg, a professor of biology at the University of Copenhagen who was not involved in the study, said that exclusomes have some similarities to micronuclei, or structures that form around chromosomal DNA that end up outside the nucleus during cell division. However, the researchers distinguished exclusomes from micronuclei because they form at different point in the cell cycle and contain no chromosomal DNA.
Understanding how cells respond to DNA outside of chromosomes may be crucial to understanding the relationship between plasmids and cancer, Regenberg said. The rings of telomere DNA are linked to cancer because they don’t shrink with cell division as they normally would and can enable the indefinite cell division that is a hallmark of the disease.
“We know that cancers and tumor cells, they will carry a big load of the circular DNA,” she told Live Science. “And that is, in some cases, actively driving the tumors.”
