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DNA damage response

Change of guard at the checkpoint

Nature Reviews Molecular Cell Biology volume 10, page 305 (2009)Cite this article

Using human cell extracts and DNA molecules with defined structures to assay ATM activation in vitro, the authors found that long double-stranded DNA (dsDNA) with blunt ends induces ATM phosphorylation (a marker of activation) more efficiently than short dsDNA with blunt ends. By contrast, dsDNA with long single-stranded overhangs (SSOs) exhibits reduced ability to activate ATM, whereas dsDNA with short SSOs activates ATM efficiently. So, the activation of ATM by DSBs is regulated by the length of both dsDNA and SSOs.

DNA fragments with SSOs contain two types of ends: those of the dsDNA region (the junctions between the dsDNA and the ssDNA) and the ends of the SSOs. By chemically blocking these different dsDNA ends, Shiotani and Zou found that only the dsDNA–ssDNA junctions are crucial for ATM activation. Notably, the dsDNA–ssDNA junctions are also known to activate ATR. So, how are the activities of ATM and ATR coordinated at DSBs?

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References

ORIGINAL RESEARCH PAPER

  1. Shiotani, B. & Zou, L. Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol. Cell 13, 547–558 (2009)

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FURTHER READING

  1. Cimprich, K. A. & Cortez, D. ATR: an essential regulator of genome integrity. Nature Rev. Mol. Cell Biol. 9, 616–627 (2008)

    Article  CAS  Google Scholar 

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Authors
  1. Francesca Cesari
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Cesari, F. Change of guard at the checkpoint. Nat Rev Mol Cell Biol 10, 305 (2009). https://doi.org/10.1038/nrm2677

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