Autophagy of germ-granule components, PGL-1 and PGL-3, contributes to DNA damage-induced germ cell apoptosis in C. elegans.

ABSTRACT: Germ granules, termed P granules in nematode C. elegans, are the germline-specific cytoplasmic structures widely observed from worms to humans. P granules are known to have critical functions for postembryonic germline development likely through regulating RNA metabolism. They are localized at the perinuclear region of germ cells during most of the developmental stages. However, the biological significance of this specific localization remains elusive. PGL-1 and PGL-3, the defining components of P granules, were shown to be lost from the perinuclear region prior to germ cell apoptosis. Furthermore, this loss was shown to be significantly enhanced upon DNA damage. Here, we show that the removal of PGL-1 and PGL-3 from the perinuclear region following UV-induced DNA damage is significantly reduced in autophagy mutants. Autophagy was previously shown to be required for DNA damage-induced germ cell apoptosis. We show that the apoptosis defect of autophagy mutants is bypassed by depletion of pgl-1 or pgl-3. These findings are consistent with time-lapse observations of LGG-1 foci formation, showing that autophagy is activated following UV irradiation and that maximal accumulation of LGG-1 foci occurs before PGL-1 removal. We also show that some of the autophagy genes are transcriptionally activated following UV irradiation by CEP-1, the worm p53-like protein. Taken together, our results indicate that autophagy is required to remove the major P granule components, PGL-1 and PGL-3, and that their removal is required for the full induction of DNA damage-induced germ cell apoptosis. Our study contributes to a better understanding of germ cell apoptosis, a process that leads to the elimination of the vast majority of germ cells in various animals from worms to mammals.

SUBMITTER: Min H 

PROVIDER: S-EPMC6534287 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature