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

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posted on 2023-06-09, 00:03 authored by Lara Barazzuol, Nicole Rickett, Limei Ju, Penny Jeggo
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.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Journal of Cell Science

ISSN

0021-9533

Publisher

Company of Biologists

Issue

19

Volume

128

Page range

3597-3606

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-01-18

First Open Access (FOA) Date

2016-01-18

First Compliant Deposit (FCD) Date

2016-01-18

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