| First Author | Barazzuol L | Year | 2015 |
| Journal | J Cell Sci | Volume | 128 |
| Issue | 19 | Pages | 3597-606 |
| PubMed ID | 26303202 | Mgi Jnum | J:233378 |
| Mgi Id | MGI:5784570 | Doi | 10.1242/jcs.171223 |
| Citation | Barazzuol L, et al. (2015) Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells. J Cell Sci 128(19):3597-606 |
| abstractText | 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 (Lig4(Y288C)), ataxia telangiectasia mutated (Atm(-/-)) and double mutant Atm(-/-)/Lig4(Y288C) 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 Lig4(Y288C) mice or that are induced by low radiation doses can activate apoptosis. A temporal analysis shows that DSB levels in Lig4(Y288C) mice diminish gradually from the embryo to a steady state level in adult mice. The neonatal SVZ compartment of Lig4(Y288C) 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. |
