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DNA repair

Small cause, large effect

Nature Reviews Cancer volume 2, page 720 (2002)Cite this article

Reporting in Genes and Development, Petrini and co-workers describe the generation of a group of hypomorphic Rad50 mutants, one of which — Rad50K22M — was used to derive so-called Rad50S/S-mutant mice. Rad50S/S mouse-embryo fibroblasts contained wild-type levels of Mre11, Nbs1 and Rad50K22M, and these components could assemble functional complexes. However, the Rad50S/S mice showed partial embryonic lethality, and those that survived were only 60% of the weight of their wild-type littermates. By 4–8 weeks of age, the mice showed signs of anaemia, and most of them died by 4 months. Of those that survived up to 7 months, 20% died from a variety of tumours.

As the premature death was associated with severe anaemia, the authors first looked more closely at haematopoietic cells in the Rad50S/S mice. At 2 weeks there was no difference between wild-type and Rad50S/S mice, but by 4 weeks of age, lymphocytes, macrophages, red blood cells and platelets were severely depleted in the mutant mice. Further experiments indicated that the progressive depletion was due to the failure of haematopoietic stem cells. Moreover, a similar depletion of cells was observed in the spermatogenic lineages of Rad50S/S mice.

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References

ORIGINAL RESEARCH PAPER

  1. Bender, C. F. et al. Cancer predisposition and hematopoietic failure in Rad50S/S mice. Genes Dev. 16, 2237–2251 (2002)

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FURTHER READING

  1. D'Amours, D. & Jackson, S. P. The Mre11 complex: at the crossroads of DNA repair and checkpoint signalling. Nature Rev. Mol. Cell Biol. 3, 317–327 (2002)

    Article  CAS  Google Scholar 

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  1. Editor, Nature Reviews Molecular Cell Biology,

    Alison Mitchell

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  1. Alison Mitchell
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Mitchell, A. Small cause, large effect. Nat Rev Cancer 2, 720 (2002). https://doi.org/10.1038/nrc910

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  • DOI: https://doi.org/10.1038/nrc910

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