Cell Biology

DNA Kills

Science Signaling  24 Feb 2009:
Vol. 2, Issue 59, pp. ec68
DOI: 10.1126/scisignal.259ec68

DNA in the cytoplasm of mammalian cells indicates an infection or gross DNA damage and, on detecting it, cells respond suicidally to stop the spread of infection. Roberts et al. have discovered that the activation of the cell-death enzymes caspase-1 and -3 in macrophages is regulated by members of a family of double-stranded DNA binding proteins. One of these, p202, dampened the caspase response, whereas another, AIM2, escalated inflammasome-dependent caspase activation. The balance of p202 and AIM2 thus provides a regulatory mechanism for DNA-dependent caspase activation in the cell and the switch for life or death.

T. L. Roberts, A. Idris, J. A. Dunn, G. M. Kelly, C. M. Burnton, S. Hodgson, L. L. Hardy, V. Garceau, M. J. Sweet, I. L. Ross, D. A. Hume, K. J. Stacey, HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 323, 1057–1060 (2009). [Abstract] [Full Text]