Cellular stress structures are packed with circular DNA

When a cell comes under pressure, from heat, toxins, or other damage, it clusters certain molecules into temporary membrane-free structures. These are stress granules. They help the cell survive and recover. How exactly these granules form and what they contain has been an active area of research.

The researchers, publishing in eLife, discovered that more than half of the nucleic acid content of stress granule cores consists of extrachromosomal circular DNA (eccDNA). This is DNA that is not packaged into chromosomes but exists freely in ring form inside the cell. EccDNA accumulates with aging and in certain diseases, and is increasingly studied as a potential marker or contributor in aging biology.

EccDNA is required for granule formation

Using CRISPR experiments in yeast cells, in which specific gene sequences are selectively disabled, the researchers showed that eccDNA is not merely present in stress granules but is actually needed for their formation. Without eccDNA, stress granules failed to assemble properly when cells were exposed to stress.

That is an unexpected result. DNA was barely anticipated in this context: stress granules were considered RNA-protein structures. This study rewrites a piece of basic cell biology about how cells respond to stress.

Connection to aging

EccDNA increases with age and is associated with genomic instability, the growing imprecision with which DNA is copied and maintained as organisms age. If eccDNA also plays a role in the cellular stress response, then changes in eccDNA levels during aging could affect how well cells handle damage. That is a preliminary interpretation, but it connects this basic biological finding to a broader question in longevity science: why do aging cells handle stress less effectively?

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