Year: 2022
Type: article
Abstract: How paternal exposure to ionizing radiation affects genetic inheritance and disease risk in the offspring has been a long-standing question in radiation biology. In humans, nearly 80% of transmitted mutations arise in the paternal germline 1 , but the transgenerational effects of ionizing radiation exposure has remained controversial and the mechanisms are unknown. Here we show that in sex-separated Caenorhabditis elegans strains, paternal, but not maternal, exposure to ionizing radiation leads to transgenerational embryonic lethality. The offspring of irradiated males displayed various genome instability phenotypes, including DNA fragmentation, chromosomal rearrangement and aneuploidy. Paternal DNA double strand breaks were repaired by maternally provided error-prone polymerase theta-mediated end joining. Mechanistically, we show that depletion of an orthologue of human histone H1.0, HIS-24, or the heterochromatin protein HPL-1, could significantly reverse the transgenerational embryonic lethality. Removal of HIS-24 or HPL-1 reduced histone 3 lysine 9 dimethylation and enabled error-free homologous recombination repair in the germline of the F 1 generation from ionizing radiation-treated P 0 males, consequently improving the viability of the F 2 generation. This work establishes the mechanistic underpinnings of the heritable consequences of paternal radiation exposure on the health of offspring, which may lead to congenital disorders and cancer in humans.
Source: Nature
Authors: Siyao Wang, David H. Meyer, Björn Schumacher
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,390
Funders: John Templeton Foundation, Oklahoma Medical Research Foundation, Deutsche Forschungsgemeinschaft, Ministry of Education, Culture, Sports, Science and Technology, Deutsche Krebshilfe, Universität zu Köln, National Institutes of Health, Horizon 2020 Framework Programme, National Center for Research Resources
Awards: G1403226871, G1515206938, G2047259676, EXC 2030: CECAD Exzellent in Alternsforschung, G2592184914, G3345895242, West German Genome Center, G394464542, G4033022399, G4353328979, G4759910570, G501936892, G509885483, G535951294, Zentrale Koordinationseinheit des Next Generation Sequencing Kompetenznetzwerks, Neuronal control of genetic inheritance and evolution, G7532160580, G7735027310, G7984235579, G8639153566, G8858395165, G8944035436
OpenAlex ID: W4312095729