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DNA repair

Variants on a theme

Nature volume 399, pages 639–640 (1999)Cite this article

Suppose you are travelling on a long car journey and come to a deep pothole in the middle of the road. You can either terminate your travels, wait for the hole to be repaired, or plunge straight across it. The last course of action is risky, but it might at least allow you to finish the trip. A similar decision has to be made when, as cells are duplicating their DNA, the replication apparatus encounters a damaged site that blocks further progress. But a dramatic development, reported by Hanaoka and colleagues1 on page 700 of this issue, reveals a mechanism that human cells use to bypass DNA damage instead of removing it. Remarkably, people who lack the enzyme that carries out one type of bypass have an inherited, cancer-prone syndrome.

Damage to a cell's genome constantly arises by the natural decay of DNA (in aqueous solution or by oxygen free-radical damage2) or by damage from external agents such as γ-rays and UV light. The result is lesions, usually in one strand of the double helix, which block progression of the enzymes that replicate DNA (the DNA polymerases). We often think of cell-cycle checkpoints — stages at which the cell-division cycle can stall — as a mechanism for cells to repair any damage in their DNA before DNA replication or division is complete. But this is not the whole story. DNA damage does not always need to be removed, and cells can divide with tremendous amounts of damage in their genomes3. How can they achieve such damage tolerance?

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Figure 1: Model for DNA synthesis across sites of damage.

References

  1. Masutani, C. et al. Nature 399, 700–704 (1999).

    Article  ADS  CAS  Google Scholar 

  2. Lindahl, T. Nature 362, 709–715 ( 1993).

    Article  ADS  CAS  Google Scholar 

  3. Spivak, G. & Hanawalt, P. C. Biochemistry 31, 6794–6800 (1992).

    Google Scholar 

  4. de Laat, W. L., Jaspers, N. G. J. & Hoeijmakers, J. H. J. Genes Dev. 13, 768– 785 (1999).

    Google Scholar 

  5. Cleaver, J. E. & Kraemer, K. H. inThe Metabolic Basis of Inherited Disease 7th edn (eds Scriver, C. R., Beaudet, A. L., Sly, W. S. & Valle, D.) 4393-4419 (McGraw-Hill, New York, 1995).

  6. Lehmann, A. et al. Proc. Natl Acad. Sci. USA 72, 219– 223 (1975).

    Google Scholar 

  7. Wang, Y.-C., Maher, V. M., Mitchell, D. L. & McCormick, J. J. Mol. Cell. Biol. 13, 4276–4283 (1993).

    Google Scholar 

  8. Cordeiro-Stone, M. et al. Biol. Chem. 272, 13945– 13954 (1997).

    Google Scholar 

  9. Svoboda, D. L., Briley, L. P. & Vos, J. M. H. Cancer Res. 58, 2445– 2448 (1998).

    Google Scholar 

  10. McGregor, W. G., Wei, D., Maher, V. M. & McCormick, J. J. Mol. Cell. Biol. 19, 147–154 ( 1999).

    Google Scholar 

  11. Cordonnier, A. M., Lehmann, A. R. & Fuchs, R. P. P. Mol. Cell. Biol. 19, 2206 –2211 (1999).

    Google Scholar 

  12. Masutani, C. et al. EMBO J. 18, 3491–3510 (1999).

    Google Scholar 

  13. Johnson, R. E., Prakash, S. & Prakash, L. Science 283, 1001– 1004 (1999).

    Google Scholar 

  14. Gibbs, P. E. et al. Proc. Natl Acad. Sci. USA 95, 6876– 6880 (1998).

    Google Scholar 

  15. Mu, D. et al. Mol. Cell. Biol. 17, 760– 769 (1997).

    Google Scholar 

Download references

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  1. Imperial Cancer Research Fund, Clare Hall Laboratories, Blanche Lane, South Mimms, EN6 3LD, Hertfordshire, UK

    Richard D. Wood

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Wood, R. Variants on a theme. Nature 399, 639–640 (1999). https://doi.org/10.1038/21323

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