Genome complexity: Removing foreign or damaged DNA (Introduction)

by David Turell , Thursday, July 12, 2018, 22:08 (2326 days ago) @ David Turell

Cells have to protect themselves from damaged DNA and foreign DNA:

https://phys.org/news/2018-07-scientists-decipher-key-features-critical.html

"The human body is built for survival. Each one of its cells is closely guarded by a set of immune proteins armed with nearly foolproof radars that detect foreign or damaged DNA.

"One of the cells' most critical sentinels is a "first responder" protein known as cGAS, which senses the presence of foreign and cancerous DNA and initiates a signaling cascade that triggers the body's defenses.

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"Specifically, the research shows that human cGAS harbors mutations that make it exquisitely sensitive to long lengths of DNA but render it "blind" or "insensitive" to short DNA fragments.

"'Human cGAS is a highly discriminating protein that has evolved enhanced specificity toward DNA," said co-first author Aaron Whiteley,

"In all mammals, cGAS works by detecting DNA that's in the wrong place. Under normal conditions, DNA is tightly packed and protected in the cell's nucleus—the cellular "safe"—where genetic information is stored. DNA has no business roaming freely around the cell. When DNA fragments do end up outside the nucleus and in the cell's cytosol, the liquid that encases the cell's organelles, it's usually a sign that something ominous is afoot, such as damage coming from within the cell or foreign DNA from viruses or bacteria that has made its way into the cell.

"The cGAS protein works by recognizing such misplaced DNA. Normally, it lies dormant in cells. But as soon as it senses the presence of DNA outside the nucleus, cGAS springs into action. It makes another chemical—a second messenger—called cGAMP, thus setting in motion a molecular chain reaction that alerts the cell to the abnormal presence of DNA. At the end of this signaling reaction, the cell either gets repaired or, if damaged beyond repair, it self-destructs.

"But the health and integrity of the cell are predicated on cGAS' ability to distinguish harmless DNA from foreign DNA or self-DNA released during cell damage and stress.

"It's a fine balancing act that keeps the immune system in equilibrium. An overactive cGAS can spark autoimmunity, or self-attack, while cGAS that fails to detect foreign DNA can lead to tumor growth and cancer development," said co-first author Wen Zhou, a postdoctoral researcher at Harvard Medical School and Dana-Farber Cancer Institute.

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"The experiments revealed that out of the 116 amino acids that differ in human and mouse cGAS, only two accounted for the altered function of human cGAS. Indeed, human cGAS was capable of recognizing long DNA with great precision but it ignored short DNA fragments. The mouse version of the protein, by contrast, did not differentiate between long and short DNA fragments.

"'These two tiny amino acids make a world of difference," Whiteley said. "They allow the human protein to be highly selective and respond only to long DNA, while ignoring short DNA, essentially rendering the human protein more tolerant of DNA presence in the cytosol of the cell."

"Plotting the genetic divergence on an evolutionary timescale, the scientists determined that the human and mouse cGAS genes parted ways sometime between 10 million and 15 million years ago.

"The two amino acids responsible for sensing long DNA and tolerating short DNA are found solely in humans and nonhuman primates, such as gorillas, chimps and bonobos."

Comment: It is obvious that damaged or foreign DNA must be stopped at all times. Therefore this cellular defense, or some other form of it, was designed along with the appearance of DNA coding or life would not have continued from the moment it began..