DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells

Lama Tarayrah-Ibraheim, Elital Chass Maurice, Guy Hadary, Sharon Ben-Hur, Alina Kolpakova, Tslil Braun, Yoav Peleg, Keren Yacobi-Sharon and Eli Arama ()
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Lama Tarayrah-Ibraheim: Weizmann Institute of Science
Elital Chass Maurice: Weizmann Institute of Science
Guy Hadary: Weizmann Institute of Science
Sharon Ben-Hur: Weizmann Institute of Science
Alina Kolpakova: Weizmann Institute of Science
Tslil Braun: Weizmann Institute of Science
Yoav Peleg: Weizmann Institute of Science
Keren Yacobi-Sharon: Weizmann Institute of Science
Eli Arama: Weizmann Institute of Science

Nature Communications, 2021, vol. 12, issue 1, 1-20

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-22622-1

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