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Expanding the functional repertoire of macrodomains

Nature Structural & Molecular Biology volume 20, pages 407–408 (2013)Cite this article

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Macrodomains are conserved globular domains that can interact with, and in some cases modify, ADP-ribose–based molecules. In this issue, two reports add to the functional repertoire of this domain, by demonstrating that a subset of macrodomain-containing proteins functions to catalyze the removal of protein-proximal ADP-ribose.

The macrodomain, a roughly 25-kDa globular domain, was originally identified in the nonhistone region of the histone variant macroH2A1 (ref. 5) and was subsequently found to be conserved throughout all kingdoms of life. In humans, ten genes encode 14 macrodomains identifiable by homology, with some proteins containing up to three of the domains6. Recent studies have implicated MDCPs in cancer, with some having oncogenic roles and others behaving as tumor suppressors7. Like ARTs, MDCPs are involved in a variety of cellular processes including transcriptional regulation and DNA-damage responses8.

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Figure 1: ADP-ribosylation is reversed by macrodomain-mediated ADP-ribosyl hydrolysis.

References

  1. Hottiger, M.O., Hassa, P.O., Lüscher, B., Schüler, H. & Koch-Nolte, F. Trends Biochem. Sci. 35, 208–219 (2010).

    Article  CAS  Google Scholar 

  2. Hassa, P.O., Haenni, S.S., Elser, M. & Hottiger, M.O. Microbiol. Mol. Biol. Rev. 70, 789–829 (2006).

    Article  CAS  Google Scholar 

  3. Jankevicius, G. et al. Nat. Struct. Mol. Biol. 20, 508–514 (2013).

    Article  CAS  Google Scholar 

  4. Rosenthal, F. et al. Nat. Struct. Mol. Biol. 20, 502–507 (2013).

    Article  CAS  Google Scholar 

  5. Pehrson, J.R. & Fried, V. Science 257, 1398–1400 (1992).

    Article  CAS  Google Scholar 

  6. Kalisch, T., Amé, J.-C., Dantzer, F. & Schreiber, V. Trends Biochem. Sci. 37, 381–390 (2012).

    Article  CAS  Google Scholar 

  7. Angelov, D. et al. Mol. Cell 11, 1033–1041 (2003).

    Article  CAS  Google Scholar 

  8. Han, W., Li, X. & Fu, X. Mutat. Res. 727, 86–103 (2011).

    Article  CAS  Google Scholar 

  9. Karras, G.I. et al. EMBO J. 24, 1911–1920 (2005).

    Article  CAS  Google Scholar 

  10. Kustatscher, G., Hothorn, M., Pugieux, C., Scheffzek, K. & Ladurner, A.G. Nat. Struct. Mol. Biol. 12, 624–625 (2005).

    Article  CAS  Google Scholar 

  11. Novikov, L. et al. Mol. Cell Biol. 31, 4244–4255 (2011).

    Article  CAS  Google Scholar 

  12. Gottschalk, A.J. et al. Proc. Natl. Acad. Sci. USA 106, 13770–13774 (2009).

    Article  CAS  Google Scholar 

  13. Ahel, D. et al. Science 325, 1240–1243 (2009).

    Article  CAS  Google Scholar 

  14. Timinszky, G. et al. Nat. Struct. Mol. Biol. 16, 923–929 (2009).

    Article  CAS  Google Scholar 

  15. Gottschalk, A.J., Trivedi, R.D., Conaway, J.W. & Conaway, R.C. J. Biol. Chem. 287, 43527–43532 (2012).

    Article  CAS  Google Scholar 

  16. Martzen, M.R. Science 286, 1153–1155 (1999).

    Article  CAS  Google Scholar 

  17. Peterson, F.C. et al. J. Biol. Chem. 286, 35955–35965 (2011).

    Article  CAS  Google Scholar 

  18. Chen, D. et al. J. Biol. Chem. 286, 13261–13271 (2011).

    Article  CAS  Google Scholar 

  19. Slade, D. et al. Nature 477, 616–620 (2011).

    Article  CAS  Google Scholar 

  20. Kim, I.-K. et al. Nat. Struct. Mol. Biol. 19, 653–656 (2012).

    Article  CAS  Google Scholar 

  21. Kleine, H. et al. Mol. Cell 32, 57–69 (2008).

    Article  CAS  Google Scholar 

  22. Wu, D. & Pan, W. Trends Biochem. Sci. 35, 161–168 (2010).

    Article  CAS  Google Scholar 

  23. Sharifi et al. EMBO J. advance online publication; doi:10.1038/emboj.2013.51 (2013).

    Article  CAS  Google Scholar 

  24. Feijs, K.L. et al. Cell Commun. Signal. 11, 5 (2013).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author would like to thank T. Zhang for critical reading of the manuscript.

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  1. Matthew J. Gamble is at the Department of Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, USA.,

    Matthew J Gamble

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  1. Matthew J Gamble
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Correspondence to Matthew J Gamble.

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Gamble, M. Expanding the functional repertoire of macrodomains. Nat Struct Mol Biol 20, 407–408 (2013). https://doi.org/10.1038/nsmb.2552

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