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DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells
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DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells
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DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells
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Journal Article
DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells
2021
Overview
During
Drosophila
embryonic development, cell death eliminates 30% of the primordial germ cells (PGCs). Inhibiting apoptosis does not prevent PGC death, suggesting a divergence from the conventional apoptotic program. Here, we demonstrate that PGCs normally activate an intrinsic alternative cell death (ACD) pathway mediated by DNase II release from lysosomes, leading to nuclear translocation and subsequent DNA double-strand breaks (DSBs). DSBs activate the DNA damage-sensing enzyme, Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) and the ATR/Chk1 branch of the DNA damage response. PARP-1 and DNase II engage in a positive feedback amplification loop mediated by the release of PAR polymers from the nucleus and the nuclear accumulation of DNase II in an AIF- and CypA-dependent manner, ultimately resulting in PGC death. Given the anatomical and molecular similarities with an ACD pathway called parthanatos, these findings reveal a parthanatos-like cell death pathway active during
Drosophila
development.
Caspase independent alternative cell death (ACD) pathways exist, but have been largely investigated under non-physiological conditions. Here, the authors show that
Drosophila
primordial germ cells normally elicit DNase II-dependent DNA damage, triggering a parthanatos-like ACD pathway.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/2
/ 13/51
/ 38/1
/ 38/35
/ 38/44
/ 38/89
/ 64
/ 64/24
/ 82/80
/ Animals
/ Animals, Genetically Modified
/ Caspase
/ Damage
/ DNA
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Embryo, Nonmammalian - cytology
/ Embryonic Development - physiology
/ Embryonic Germ Cells - cytology
/ Embryonic Germ Cells - physiology
/ Endodeoxyribonucleases - genetics
/ Endodeoxyribonucleases - metabolism
/ Female
/ Humanities and Social Sciences
/ Insects
/ Male
/ Poly (ADP-Ribose) Polymerase-1 - genetics
/ Poly (ADP-Ribose) Polymerase-1 - metabolism
/ Poly Adenosine Diphosphate Ribose - metabolism
/ Polymers
/ Ribose
/ Science
