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Zombie gene protects against cancer in elephants
Dead gene reborn helps destroy cells with damaged DNA

An estimated 17 percent of humans worldwide die from cancer, but less than five percent of captive elephants—who also live for about 70 years, and have about 100 times as many potentially cancerous cells as humans—die from the disease.

It was thought that bigger animals have vastly more cells, and they tend to live longer, which means more time and opportunities to accumulate cancer-causing mutations. But in the study, it suggests elephants may have protection from cancer because of a unique "zombie" gene.

Three years ago, research teams from the University of Chicago and the University of Utah, working separately, began to unravel why. They knew that humans, like all other animals, have one copy of the master tumor suppressor gene p53. This gene enables humans and elephants to recognise unrepaired DNA damage, a precursor of cancer. Then it causes those damaged cells to die.

Unexpectedly, however, the researchers found that elephants have 20 copies of p53. This makes their cells significantly more sensitive to damaged DNA and quicker to engage in cellular suicide.

Published in Cell Reports, the University of Chicago team describes a second element of this process: an anti-cancer gene that returned from the dead.

“Genes duplicate all the time,” said Vincent Lynch, assistant professor of human genetics at the University of Chicago and the study’s senior author. “Sometimes they make mistakes, producing non-functional versions known as pseudogenes. We often refer to these dismissively as dead genes.”

While studying p53 in elephants, however, Lynch and colleagues found a former pseudogene called leukemia inhibitory factor 6 (LIF6) that had somehow evolved a new on-switch. LIF6, back from the dead, had become a valuable working gene. Its function, when activated by p53, is to respond to damaged DNA by killing the cell. The LIF6 gene makes a protein that goes, quite rapidly, to the mitochondria, the cell’s main energy source. That protein pokes holes in the mitochondria, causing the cell to die.

“Hence, zombie,” said Lynch. “This dead gene came back to life. When it gets turned on by damaged DNA, it kills that cell, quickly. This is beneficial, because it acts in response to genetic mistakes, errors made when the DNA is being repaired. Getting rid of that cell can prevent a subsequent cancer.”

Elephants have eight LIF genes, but only LIF6 is known to be functional. Although it was only recently described, it appears to have been helping elephants and their relatives for a long time.

Exactly how LIF6 induces apoptosis, however, remains unclear. This will be “the focus of continued studies,” the authors wrote.

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APBN Editorial Calendar 2018
January:
Obesity / Outlook for 2018
February:
Searching for the fountain of youth
March:
Women in Science - Making a difference
April:
Digestive health in the 21st century - Trust your guts
May:
Dental health - The root to good health
June:
Cancer - Therapies and strategies for better patient outcomes
July:
Water management - Technologies for biotech and pharmaceutical industries
August:
Regenerative technology - Meat of the future
September:
Doctor Robot - The digital healthcare revolution
October:
Bones / Breast cancer
November:
Liver health / Top science research nations & institutions
December:
AIDS / Breakthrough of the year/Emerging trends
Editorial calendar is subjected to changes.
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