Science: Reveals the mechanism by which protein BAF prevents cells from attacking their own DNA.

August 18, 2020 /--- virus proliferates by injecting its DNA into host cells.
once it enters the cell fluid, the foreign material triggers a defense mechanism called the cGAS-STING pathway.
a protein called cyclic GMP-AMP lysase (cGAS) is also present in the liquid, which binds to invading DNA to produce a new molecule.
this is then combined with another protein called STING, which induces an inflammatory immune response.
time, the substances contained in the liquid -- and those in contact with the cGAS protein -- come not from the virus, but from the cells themselves, such as after an accidental rupture of the nucleus.
when this happens, the cGAS-STING pathway is not activated.
now, in a new study, researchers from the Federal Institute of Technology (EPFL) in Lausanne, Switzerland, have confirmed how cells react differently to their DNA and genetic material from pathogens to avoid attacking the wrong target.
their findings provide new insights into the complex processes that occur in the body's inflammatory response.
study was published in the August 14, 2020 issue of the Journal of Science under the title "BAF restricts cGAS on nuclear DNA to prevent innate immune activation".
author of the paper is Professor Andrea Ablasser of the Federal Institute of Technology in Lausanne, Switzerland.
images from Delft University of Technology.
Ablasser and his team have come up with new insights into the key role of a small protein called the Barrier-to-Autointegration Factor (BAF).
found that by binding to harmless DNA, BAF prevents cGAS proteins from binding to DNA, thereby preventing cGAS-STING pathway activation.
BAF enhances the function of the nucleosis, connecting the nucleofilm to the internal DNA.
experiments have shown that when the protein is removed from laboratory-grown cells, the nucleation of the cell ruptures.
this rupture releases genetic material into the in-cell fluid, where it is in contact with the cGAS protein and triggers the cGAS-STING pathway as if it were foreign DNA.
many ways to break the nucleation of a cell, such as applying mechanical pressure.
only one way, according to the paper's co-lead author, Baptiste Guey, --- removing the BAF protein --- cause an immune response.
, "So we can conclude that BAF plays a key role in preventing cells from attacking their DNA."
" inhibition of this protein is extremely important: while the cGAS-STING approach helps the body fight infection, it also needs to be controlled.
the nuclei occasionally ruptured, but cells can repair damage," said Marilyna Wischnewski, co-lead author of the paper.
if cGAS were to bind to DNA every time, the consequences would be even worse.
the "overactive cGAS-STING pathway can be observed in Aicardi-Goutières syndrome."
rare and often fatal genetic disorder induces an excessive inflammatory response, just as cells in the body are constantly attacked by invading pathogens.
BF is also thought to play a role in certain types of tumours.
, according to Wischnewski, high concentrations of BAF in cancer cells may be associated with poor prognosm.
explained, "It could be BAF that makes the tumor more resistant."
by preventing the activation of the cGAS-STING pathway, it may cause cancer cells to evade the body's immune system.
" protein exists in different numbers in different types of cells.
the researchers plan to delve into these quantitative changes as they try to understand how different tissue types respond to infection and inflammation.
(bioon.com) Reference: 1.Baptiste Guey et al. BAF restricts cGAS on nuclear DNA to prevent innate immune activation. Science, 2020, doi:10.1126/science.aaw6421.How a protein stops cells from attacking their own DNA.