News Releases & Research Results Elucidation of the mechanism by which the foreign DNA sensor cGAS for innate immunity does not respond to autologous chromosomal DNA - A clue to elucidating the causes of diseases such as viral infection protection, autoimmune diseases, cancer, and neurodegenerative diseases -

The results of collaborative research conducted by Professor Hitoshi Kurumizaka of the Institute for Quantitative Biosciences, the University of Tokyo, and Professor Hironori Funabiki of the Rockefeller University (USA).

• The molecular mechanism by which the DNA sensor “cGAS” for innate immunity is inactivated by nucleosomes* was elucidated by combining biochemical analysis with three-dimensional structural analysis with the latest cryo-electron microscope.
  *Basic structural unit of a chromosome, responsible for DNA folding.
• In the presence of DNA and nucleosomes, cGAS was demonstrated to selectively bind to nucleosomes rather than DNA, thereby suppressing autologous immune- and inflammatory response-inducing activities.
• The results of this research project should facilitate the elucidation of the causes of cGAS-associated viral infections, autoimmune diseases, cancer, aging, and neurodegenerative diseases and the establishment of their treatment methods.

This program was conducted with the support of the Platform Project for Supporting in Drug Discovery and Life Science Research (BINDS) by AMED.

The results of this research project were published online as a brief paper in the American scientific journal Science on September 11.

Kujirai T., et al. Structural basis for the inhibition of cGAS by nucleosomes Science
DOI: 10.1126/science.abd0237