University of Edinburgh researchers report that they discovered how damage to cells' DNA can cause inflammation, which causes the body to get rid of damaged cells and keep tissues healthy.
The study (“cGAS Surveillance of Micronuclei Links Genome Instability to Innate Immunity”), which appears in Nature, sheds new light on how potentially cancerous cells are flagged, so that they can be removed as part of the body's natural surveillance systems before tumors form, according to the team.
“DNA is strictly compartmentalized within the nucleus to prevent autoimmunity; despite this, cyclic GMP–AMP synthase (cGAS), a cytosolic sensor of double-stranded DNA, is activated in autoinflammatory disorders and by DNA damage,” write the investigators. “Here, we report that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells.”
“As DNA damage is often one of the early steps in the development of cancer, the detection of micronuclei by cGAS could therefore be an important early alarm system allowing the human body to detect and remove potentially cancerous cells.”
The researchers also believe their findings could open the door to understanding how inflammation occurs in certain types of autoinflammatory diseases, where the immune system attacks the body's own tissues.
“Our findings provide a possible new mechanism for how the body protects itself against cancer, but in some circumstances could instead trigger inflammatory disease,” says lead author Karen Mackenzie, Ph.D.
“We hope that this research will inform future studies into the development of improved therapeutic approaches,” adds Martin Reijns, Ph.D., senior research fellow.