Biological complexity: protecting cell DNA from auto-attack (Introduction)

by David Turell , Thursday, August 13, 2020, 22:12 (1353 days ago) @ David Turell

DNA loose from the nucleus will be attacked by cellular defense mechanisms unless a backup defense steps in:

https://phys.org/news/2020-08-protein-cells-dna.html

"Viruses multiply by injecting their DNA into a host cell. Once it enters the intracellular fluid, this foreign material triggers a defense mechanism known as the cGAS-STING pathway. The protein cyclic GMP-AMP Synthase (cGAS), which is also found inside the fluid, binds to the invading DNA to create a new molecule. This, in turn, binds to another protein called Stimulator of Interferon Genes (STING), which induces an inflammatory immune response.

"Sometimes, the material contained inside the fluid—and in contact with the cGAS protein—comes not from a virus but from the cell itself, for instance after the nucleus has accidentally ruptured. When this happens, the cGAS-STING pathway isn't activated. Scientists at EPFL have demonstrated how cells are able to respond differently to their own DNA and to genetic material from a pathogen—and avoid attacking the wrong target. Their discovery, published in a paper in the journal Science, sheds new light on the complex processes at work in the body's inflammatory response.

"The team, led by Prof. Andrea Ablasser and working with colleagues from the laboratories of Prof. Beat Fierz and Prof. Selman Sakar, uncovered new insights into the key role of a small protein known as Barrier-to-Autointegration Factor (BAF). They showed that, by binding to the inoffensive DNA, BAF prevents the cGAS protein from doing the same, thereby stopping the cGAS-STING pathway in its tracks.

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"There are various ways to cause a nucleus to rupture, such as by applying mechanical pressure. But according to Baptiste Guey, one of the paper's lead authors, only one of these methods—removing the BAF protein—induces an immune response. "We can therefore conclude that BAF plays a key role in preventing the cell from attacking its own DNA," says Guey.

"The protein's inhibitor role is vitally important: Although the cGAS-STING pathway helps the body fight off infections, it also needs to be kept in check. "Nuclei do occasionally rupture, but cells are able to repair the damage," says Marilena Wischnewski, another lead author of the paper. "If cGAS bound to the DNA every time that happened, the consequences would be more serious."

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"The protein is found in varying quantities in different types of cells. The team is planning to dig deeper into these variations as they seek to understand how different tissue types respond to infection and inflammation."

Comment: this is another protective mechanism that had to be designed and in place when when organisms appeared in evolution. Too complex for chance development.