Adult stem cells are often exposed to genotoxic stress, whether directly from the environment or from within their own stem cell niche. DNA damage accumulates in the stem cells of aged tissues and has been proposed to accelerate both cellular aging and cancer formation, yet the mechanism through which this occurs is not well understood. Now, on p. 4312, Ting Xie and colleagues investigate this issue and demonstrate that DNA damage disrupts germline stem cell (GSC) self-renewal and lineage differentiation in a checkpoint kinase 2 (CHK2)-dependent manner. The authors use an inducible system to generate widespread double-stranded breaks (DSBs) in the GSCs of the Drosophila ovary. These DSBs resolve over time but leave the tissue with significantly fewer GSCs. By contrast, the number of GSC daughter cells initially increases then remains constant, suggesting that differentiation is blocked. The authors go on to identify a role for CHK2, showing how the induction of DSBs in flies lacking CHK2 is sufficient to prevent damage-induced GSC loss. Finally, the authors provide some evidence to suggest that the loss of GSCs may be partly due to reduced BMP signalling and cell adhesion. This study offers insight into how DNA damage might affect stem cell-based tissue regeneration and provides a mechanistic target – CHK2 – for further investigation.
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