Kanazawa University Scientists Observe Enzymes Breaking Down DNA in Real Time

Researchers at Kanazawa University's Nano Life Science Institute (WPI-NanoLSI) have directly visualized how enzymes find and break apart DNA molecules in real time. Using high-speed atomic force microscopy (HS-AFM), the team observed individual enzymes moving along DNA and repeatedly returning to vulnerable regions before fragmentation occurred. These findings elucidate how DNA's structure influences its susceptibility to enzymatic breakdown.

The research focused on enzymes like DNase I, which helps clear DNA released from damaged or dying cells, a process implicated in inflammatory and autoimmune diseases when malfunctioning. While the chemistry of DNase I is well-understood, observing its precise interaction with DNA at the molecular level had been challenging.

The HS-AFM observations revealed that DNase I did not interact uniformly with DNA. The enzyme frequently stayed near exposed DNA ends and curved regions, often returning to these areas before causing a break. Based on these patterns, the researchers developed a conceptual framework named STORM (Scan – Target – Occupy – Rupture – Mobilize) to describe the observed interaction stages.

Furthermore, the study demonstrated that tightly packed DNA resists degradation. DNA condensed by protamine, particularly into compact toroidal structures, showed significant resistance to DNase I. These structures remained intact for extended periods, suggesting that the physical organization of DNA, rather than just electrostatic interactions, creates a barrier limiting enzyme access.