A team of researchers studying the one-celled organism Tetrahymena has discovered a cellular structure that acts as a selective garbage disposal for unneeded DNA. The recently identified cellular component, dubbed a "dumposome," may prove to be an entirely new organelle. It's introduced in the cover story of the October 4 issue of Cell.
"The dumposome surrounds the DNA it's gobbling up, and then spits it out of the nucleus," says C. David Allis, the University of Rochester professor of biology who led the group of researchers. "It's basically a little garbage disposal for eating extra DNA."
Dumposomes appear only briefly during the life cycle of Tetrahymena. Over a five-hour period during reproduction, molecules of a structural protein known as Pdd1p coalesce to form about a dozen circular dumposomes -- each only one- thousandth of a millimeter in diameter -- on the inner edge of the nucleus.
"When Tetrahymena nuclei are examined during reproduction, they look like cereal bowls with floating Cheerios clinging to their inner edges," Allis says. "But these 'Cheerios' are actually dumposomes that are breaking down DNA within their middles."
"Other researchers had thought that the structure was just a developing nucleolus, which is the part of the nucleus that is a workbench for building ribosomes," adds James Smothers, a graduate student in Allis' lab. "We now know that the structure is unique with a distinct function -- which could make it an organelle in its own right."
Although it has only one cell, the mature Tetrahymena has two nuclei. One of these acts as a permanent genetic library; its DNA is left intact and is passed along to offspring. The second nucleus carries the DNA used by the organism during its own lifetime. The dumposomes break down 15 to 20 percent of this DNA during reproduction.
The idea of selective DNA removal is not new: Researchers have observed it in many organisms, including worms, insects, and fish, but not humans. But Pdd1p is the first protein to be linked to this kind of DNA removal, and the dumposome is the first cellular component biologists have implicated in DNA elimination. Scientists had expected that the process would involve genetic markers that identify the doomed DNA, molecular scissors to snip it out, and enzymes to degrade it (all of which Allis suspects work in tandem with dumposomes), but they did not anticipate finding a separate structure devoted to DNA degradation.
Dumposomes seem to target heterochromatin, a distinct form of highly repetitive DNA that contains few active genes. "It's been said that heterochromatin is a bad neighborhood for good genes," Smothers says. "Such inactive regions might just be trashed in the name of streamlining. But it's also possible that these genes are of use only during reproduction and are thrown away afterward."
The PDD1 gene was cloned by Malavi Madireddi, a former Rochester graduate student now at Columbia-Presbyterian Cancer Center in New York, and Robert Coyne of the Fred Hutchinson Cancer Research Center in Seattle. Two other Hutchinson Center researchers also contributed: Katherine Mickey, who developed the fluorescent hybridization techniques that permitted visualization of Pdd1p, and Meng-Chao Yao, an expert in the DNA sequences that are thought to promote DNA removal. Smothers conducted the electron microscopy of dumposomes at Syracuse University. The research was funded by the National Institutes of Health.