Depletion of endonuclease G selectively kills polyploid cells.

Endonuclease G is a mitochondrio-nuclear located nuclease with dual-vital and lethal-functions. Besides its role in apoptosis execution, we have recently shown that depletion of endonuclease G leads to necrotic cell death in yeast. Here, we present further mechanistic elucidation of endonuclease G's vital functions. The deletion of the yeast Endonuclease G gene causes the complete elimination of tetraploid cells during exponential growth. Consistently, conditional knockdown of mammalian endonuclease G selectively kills tetraploid but not diploid clones of the human HCT116 colon carcinoma cell line. We conclude that endonuclease G is important for the viability of polyploid mammalian and yeast cells.