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DNA repair

Working on different ends

Nature Reviews Molecular Cell Biology volume 9, page 423 (2008)Cite this article

...the chemical nature of the DNA break ends determines the DNA repair pathway.

DSBs are induced by exposing cells to ionizing radiation (IR) that breaks the DNA in several ways and causes 'ragged' DNA-end structures, whereas enzymatic DNA cleavage produces DSBs with chemically defined 'clean' ends (with a terminal 3′- or 5′-hydroxyl group). By monitoring the recruitment of checkpoint and recombination proteins to nuclear foci (the sites of DNA repair) the authors demonstrated that a fraction of the DNA lesions induced by IR in G1 is not repaired by NHEJ but is processed to generate single-stranded (ss) DNA regions that are coated by replication protein A (RPA). These structures persist until S phase, when they are repaired by the HR machinery. Similar experiments showed that, unlike the IR-induced DSBs, endonuclease-induced DSBs are not processed to form RPA-bound ssDNA structures until S phase, so cells must have a way to discriminate between ragged and clean DSBs.

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References

ORIGINAL RESEARCH PAPER

  1. Barlow, J. H., Lisby, M. & Rothstein, R. Differential regulation of the cellular response to DNA double-strand breaks in G1. Mol. Cell 30, 73–85 (2008)

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FURTHER READING

  1. Branzei, D. & Foiani, M. Regulation of DNA repair throughout the cell cycle. Nature Rev. Mol. Cell Biol. 9, 297–308 (2008)

    Article  CAS  Google Scholar 

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Authors
  1. Francesca Cesari
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Cesari, F. Working on different ends. Nat Rev Mol Cell Biol 9, 423 (2008). https://doi.org/10.1038/nrm2411

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