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The fate of cells undergoing spontaneous DNA damage during development

Miermont, A; Antolović, V; Lenn, T; Nichols, JME; Millward, LJ; Chubb, JR; (2019) The fate of cells undergoing spontaneous DNA damage during development. Development , 146 (12) , Article dev174268. 10.1242/dev.174268. Green open access

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Abstract

Embryonic development involves extensive and often rapid cell proliferation. An unavoidable side effect of cell proliferation is DNA damage. The consequences of spontaneous DNA damage during development are not clear. Here we define an approach to determine the effects of DNA damage on cell fate choice. Using single cell transcriptomics, we identified a sub-population of Dictyostelium cells experiencing spontaneous DNA damage. Damaged cells displayed high expression of rad51, with the gene induced by multiple types of genotoxic stress. Using live imaging, we tracked high Rad51 cells from differentiation onset until cell fate assignment. High Rad51 cells were shed from multicellular structures, excluding damaged cells from the spore population. Cell shedding resulted from impaired cell motility and defective cell-cell adhesion, with damaged cells additionally defective in activation of spore gene expression. These data indicate DNA damage is not insulated from other aspects of cell physiology during development and multiple features of damaged cells prevent propagation of genetic error. Our approach is generally applicable for monitoring rare sub-populations during development, and permits analysis of developmental perturbations occurring within a physiological dynamic range.

Type: Article
Title: The fate of cells undergoing spontaneous DNA damage during development
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.174268
Publisher version: https://doi.org/10.1242/dev.174268
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Cell-cell adhesion, DNA damage, Dictyostelium, Single cell transcriptomics, Stochastic gene expression
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10072652
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