Civil war inside our cells: Scientists show how our bodies fight off "jumping genes"

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There’s a civil war going on inside every one of the 37 trillion cells in your body. Now, University of Michigan scientists have uncovered how your cells keep this war from causing too much collateral damage.On one side of the battle: your “regular” DNA, which provides the day-to-day instructions for life. On the other side: tiny bits of rogue DNA that hide like spies between genes in your own DNA. From time to time, these rogue bits of DNA spin off a copy of themselves and “jump” to another DNA location — often causing harmful mutations when they land.How our cells fight off the effects of these rogue DNAs, called LINE-1 retrotransposons, has remained a mystery. But in a new paper published in the open-access journal eLife, scientists from the University of Michigan Medical School and Howard Hughes Medical Institute and colleagues have captured the action like battlefield reporters.They zeroed in on the defensive activity of an enzyme called APOBEC3A — and showed that it can cause mutations within the LINE-1 retrotransposons as they jump to new locations. This prevents subsequent invasions into other areas of DNA.This defensive strike sends out a signal to other defense forces inside the cell, which neutralize the jumping gene and sweep away the destroyed copy.The findings not only help explain a mystery of the body — they also may help in the development of cancer drugs. That’s because other APOBEC enzymes cause cancer-related mutations — a kind of “friendly fire” that makes these enzymes a potential target for new drugs.The new findings about APOBEC3A’s ability to squelch LINE-1 activity could mean that blocking APOBEC3 with new cancer drugs might carry consequences.John Moran, Ph.D., the U-M and HHMI geneticist who led the work with Sandra Richardson, Ph.D., says the new finding gives scientists the first proof of a hypothesized defense strategy.”It’s often hard to see what normally happens during an efficient process that occurs inside our cells,” he explains. “But by blocking the process that would normally clean up the evidence of this interaction, we can start to see what is going on.”Dangerous junkOur cells may each contain as many as 500,000 copies of LINE-1, says Moran, the Gilbert S. Omenn Collegiate Professor of human genetics and professor of internal medicine at U-M and an HHMI research investigator.LINE-1 is part of the so-called “junk DNA” that makes up half of our genetic material — but the purpose of “junk DNA” is unclear.Most LINE-1 copies lay dormant, but a few dozen active copies reside in each cell. LINE-1 retrotransposons can activate and jump, making them dangerous junk.In fact, LINE-1 alone may cause one in every 250 disease-causing mutations in humans.So, the “junk” moniker doesn’t really fit, says Moran — though he admits we are probably stuck with this label. …


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