Endonuclease G Regulates Budding Yeast Life and Death

Abstract

Endonuclease G (EndoG) is located in mitochondria yet translocates into the nucleus of apoptotic cells during human degenerative diseases. Nonetheless, a direct involvement of EndoG in cell-death execution remains equivocal, and the mechanism for mitochondrio-nuclear translocation is not known. Here, we show that the yeast homolog of EndoG (Nuc1p) can efficiently trigger apoptotic cell death when excluded from mitochondria. Nuc1p induces apoptosis in yeast independently of metacaspase or of apoptosis inducing factor. Instead, the permeability transition pore, karyopherin Kap123p, and histone H2B interact with Nuc1p and are required for cell death upon Nuc1p overexpression, suggesting a pathway in which mitochondrial pore opening, nuclear import, and chromatin association are successively involved in EndoG-mediated death. Deletion of NUC1 diminishes apoptotic death when mitochondrial respiration is increased but enhances necrotic death when oxidative phosphorylation is repressed, pointing to dual--lethal and vital--roles for EndoG.

The role of DNA exonucleases in protecting genome stability and their impact on ageing

“…In addition to the intrinsic proofreading nuclease activity of POLG, in S. cerevisiae the endo/exonuclease Nucp1 (Dake et al 1988;Vincent et al 1988) is the major nuclease in yeast mitochondria and is involved in a number of functions including mitochondrial DNA metabolism, recombination and cell death (Buttner et al 2007;Zassenhaus and Denniger 1994). Nucp1 can degrade ssRNA and has DNA endonuclease activity (on both ssDNA and dsDNA) and 5′-3′ exonuclease activity (on dsDNA).…”

Depletion of Endonuclease G Selectively Kills Polyploid Cells

“…This finding is consistent with the observed loss of viability of yeast cells upon EndoG disruption. 25 Hence, mammalian as well as yeast EndoG seem to function in a process necessary for survival. Remarkably, the necessity of EndoG to maintain viability is largely enhanced in tetraploid cells.…”

“…25,26,31 In addition, EndoG has been suspected to have genuine, vital functions in mouse and yeast that have been poorly investigated. In this study we show that, besides protecting against necrotic cell death, 25 EndoG is essential for the maintenance of polyploid cells.…”

“…. 25,26 Beyond its role in apoptosis execution, EndoG has been shown to be necessary for normal cell cycle progression. Thus, its absence leads to an arrest in G 2 phase in mammalian as well as yeast cells.…”

“…Thus, its absence leads to an arrest in G 2 phase in mammalian as well as yeast cells. 25,27 Furthermore, EndoG may contribute to homologous recombination. A recent study has demonstrated that depletion of cellular EndoG levels reduces the frequency of recombination events in the herpes simplex virus-1 a (HSV-1a) sequence.…”