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SARM1 as a dsDNA detector to sense nuclear damage and viruses to drive cell death

Adel Avetisyan1, Ernesto Manzo1, Marc R Freeman1

  • 1Vollum Institute, OHSU, Portland, OR, USA.

Molecular Cell
|December 19, 2025
PubMed

Insights

The enzyme SARM1, a NAD+ hydrolase, can bind to double-stranded DNA (dsDNA). This discovery suggests SARM1 may play a role in sensing DNA damage and initiating cell death pathways.

Area of Science:

  • Molecular biology
  • Cellular biology
  • Neuroscience

Background:

  • The enzyme SARM1 is known to be involved in neurodegenerative processes.
  • SARM1 functions as a NAD+ hydrolase, depleting NAD+ levels.

Purpose of the Study:

  • To investigate the regulatory mechanisms of SARM1.
  • To explore novel functions of SARM1 beyond its known role in degeneration.

Main Methods:

  • Biochemical assays to test SARM1 binding to dsDNA.
  • Enzyme activity assays to measure SARM1 activation by dsDNA.

Main Results:

  • SARM1 directly binds to double-stranded DNA (dsDNA).
  • dsDNA binding activates SARM1's NAD+ hydrolase activity.
  • This activation links SARM1 to potential roles in DNA damage and viral sensing.

Conclusions:

  • SARM1 acts as a sensor for dsDNA, integrating DNA damage or viral detection with cell death.
  • This finding opens new avenues for understanding SARM1's role in cellular homeostasis and disease.

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