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Genome integrity in primordial germ cells (PGCs) is a prerequisite for fertility and species maintenance. In C. elegans, PGCs require global-genome nucleotide excision repair (GG-NER) to remove UV-induced DNA lesions. Failure to remove the lesions leads to the activation of the C. elegans p53, CEP-1, resulting in mitotic arrest of the PGCs. We show that the eIF4E2 translation initiation factor IFE-4 in somatic gonad precursor (SGP) niche cells regulates the CEP-1/p53-mediated DNA damage response (DDR) in PGCs. We determine that the IFE-4 translation target EGL-15/FGFR regulates the non-cell-autonomous DDR that is mediated via FGF-like signaling. Using hair follicle stem cells as a paradigm, we demonstrate that the eIF4E2-mediated niche cell regulation of the p53 response in stem cells is highly conserved in mammals. We thus reveal that the somatic niche regulates the CEP-1/p53-mediated DNA damage checkpoint in PGCs. Our data suggest that the somatic niche impacts the stability of heritable genomes.
This article was published in the following journal.
Name: Developmental cell
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The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.
The response of cells in sensing a difference in OSMOTIC PRESSURE between the inside and outside of the cell. This response includes signaling from osmotic sensors to activate transcription factors, which in turn regulate the expression of osmocompensatory genes, all functioning to maintain CELL VOLUME and the water concentration inside the cells.
A radiation-protective agent that can inhibit DNA damage by binding to the DNA. It also increases the susceptibility of blood cells to complement-mediated lysis.
A highly-conserved family of protein serine-threonine kinases that regulate the CELL CYCLE; MITOSIS; and the response to DNA DAMAGE. They are also involved in the assembly and function of microtubule-based structures such as CILIA and CENTRIOLES.
The process of embryo initiation in culture from vegetative, non-gametic, sporophytic, or somatic plant cells.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Fertility is the ability of a couple to conceive, but can related to specifically the man or woman. Various reasons can cause a couple to be infertile, and due to the strong desire of these patients to have <!--LGfEGNT2Lhm-->children, a range of ...