4.8 Article

Somatic PMK-1/p38 signaling links environmental stress to germ cell apoptosis and heritable euploidy

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NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41467-022-28225-8

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资金

  1. (Ministry of Education, Culture, Sports, Science and Technology, Japan)
  2. NIH National Center for Research Resources, US
  3. Cologne Cardiovascular Research Center (CCRC)
  4. Deutsche Forschungsgemeinschaft [SCHU 2494/3-1, SCHU 2494/7-1, SCHU 2494/10-1, SCHU 2494/11-1, CECAD EXC 2030 - 390661388, SFB 829, SFB 670, KFO 286, KFO 329, GRK 2407]
  5. Deutsche Krebshilfe [70112899]
  6. H2020-MSCA-ITN-2018
  7. John Templeton Foundation [61734]

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This study reveals that stress signaling from intestinal cells regulates elimination of germ cells carrying damaged genomes, which in turn impacts inheritance. Failure of intestinal signaling results in stress-induced aneuploidy.
Inheritance of stable and euploid genomes is a prerequisite for species maintenance. The DNA damage response in germ cells controls the integrity of heritable genomes. Whether and how somatic stress responses impact the quality control of germline genomes has remained unclear. Here, we show that PMK-1/p38-mediated stress signaling in intestinal cells is required for germ cell apoptosis amid ionizing radiation (IR)-induced or meiotic DNA double strand breaks (DSBs) in C. elegans. We demonstrate that intestinal PMK-1/p38 signaling regulates the germ cell death in response to environmental stress. The PMK-1/p38 target SYSM-1 is secreted from the intestine into the germline to trigger apoptosis of meiotic pachytene cells. Compromised PMK-1/p38 signaling in intestinal cells leads to stress-induced aneuploidy in the consequent generation. Our data suggest that somatic stress surveillance controls heritable genome integrity and euploidy. Here the authors show that elimination of germ cells carrying damaged genomes is regulated by intestinal stress signalling in nematodes. Failure of the intestinal signalling results in stress-induced aneuploidy indicating that environmental stress impacts inheritance.

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