AI Article Synopsis
- The process of embryogenesis depends on the ability of organisms to handle DNA damage and remove defective cells to ensure survival.
- In Drosophila embryos, nuclei with high DNA damage trigger a programmed elimination process known as nuclear fallout during development.
- This study identifies a Chk2-dependent mechanism that retains certain mRNAs in the nucleus to prevent the production of essential proteins, with specific attention to histone messages and their regulation by Chk2, highlighting the intricate DNA damage response systems that protect genome integrity in eukaryotes.
Article Abstract
The faithful execution of embryogenesis relies on the ability of organisms to respond to genotoxic stress and to eliminate defective cells that could otherwise compromise viability. In syncytial-stage Drosophila embryos, nuclei with excessive DNA damage undergo programmed elimination through an as-yet poorly understood process of nuclear fallout at the midblastula transition. We show that this involves a Chk2-dependent mechanism of mRNA nuclear retention that is induced by DNA damage and prevents the translation of specific zygotic mRNAs encoding key mitotic, cytoskeletal, and nuclear proteins required to maintain nuclear viability. For histone messages, we show that nuclear retention involves Chk2-mediated inactivation of the Drosophila stem loop binding protein (SLBP), the levels of which are specifically depleted in damaged nuclei following Chk2 phosphorylation, an event that contributes to nuclear fallout. These results reveal a layer of regulation within the DNA damage surveillance systems that safeguard genome integrity in eukaryotes.
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| http://dx.doi.org/10.1016/j.devcel.2014.03.025 | DOI Listing |
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