Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells

Barazzuol, Lara, Rickett, Nicole, Ju, Limei and Jeggo, Penny A (2015) Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells. Journal of Cell Science, 128 (19). pp. 3597-3606. ISSN 0021-9533

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Abstract

The embryonic neural stem cell compartment is characterised by rapid proliferation from embryonic day (E)11 to E16.5, high endogenous DNA double-strand break (DSB) formation and sensitive activation of apoptosis. Here, we ask whether DSBs arise in the adult neural stem
cell compartments, the sub-ventricular zone (SVZ) of the lateral ventricles and the sub-granular zone (SGZ) of the hippocampal dentate gyrus, and whether they activate apoptosis. We used mice with a hypomorphic mutation in DNA ligase IV (Lig4Y288C), ataxia telangiectasia mutated (Atm−/−) and double mutant Atm−/−/Lig4Y288C mice. We demonstrate that, although DSBs do not arise at a high frequency in adult neural stem cells, the low numbers of DSBs that persist endogenously in Lig4Y288C mice or that are induced by low radiation doses can activate apoptosis. A temporal analysis shows that DSB levels in Lig4Y288C mice diminish gradually from the embryo to a steady state level in adult mice. The neonatal SVZ compartment of Lig4Y288C mice harbours diminished DSBs compared to its differentiated counterpart, suggesting a process selecting against unfit stem cells. Finally, we reveal high endogenous apoptosis in the developing SVZ of wild-type newborn mice.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Penny Jeggo
Date Deposited: 18 Jan 2016 11:59
Last Modified: 06 Mar 2017 14:10
URI: http://sro.sussex.ac.uk/id/eprint/59270

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