Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Modulation of DNMT1 activity by ADP-ribose polymers

Oncogene volume 24, pages 13–19 (2005)Cite this article

Abstract

We provided evidence that competitive inhibition of poly(ADP-ribose) polymerases in mammalian cells treated with 3-aminobenzamide causes DNA hypermethylation in the genome and anomalous hypermethylation of CpG islands. The molecular mechanism(s) connecting poly(ADP-ribosyl)ation with DNA methylation is still unknown. Here we show that DNMT1 is able to bind long and branched ADP-ribose polymers in a noncovalent way. Binding of poly ADP-ribose on DNMT1 inhibits DNA methyltransferase activity. Co-immunoprecipitation reactions indicate that PARP1 and DNMT1 are associated in vivo and that in this complex PARP1 is present in its ADP-ribosylated isoform. We suggest that this complex is catalytically inefficient in DNA methylation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Aboul-Ela N, Jacobson E and Jacobson MK . (1988). Anal. Biochem., 174, 239–250.

  • Althaus FR, Bachmann S, Hofferer L, Kleczkowska HE, Malanga M, Panzeter PL, Realini CA and Zweifel B . (1995). Biochimie, 77, 423–432.

    Article  CAS  Google Scholar 

  • Amé JC, Jacobson EL and Jacobson MK . (2000). From DNA Damage and Stress Signalling to Cell Death: Poly ADP-Ribosylation Reactions De Murcia G and Shall S (eds). Oxford University Press: New York, pp. 1–34.

    Google Scholar 

  • Antequera F and Bird A . (1993). Proc. Natl. Acad. Sci. USA, 90, 11995–11999.

  • Bestor TH . (2000). Hum. Mol. Genet., 9, 2395–2400.

  • Bestor TH and Verdine GL . (1994). Curr. Opin. Cell Biol., 6, 380–389.

  • Bird AP . (1986). Nature, 321, 209–213.

    Article  CAS  Google Scholar 

  • Bird AP . (1992). Cell, 70, 5–8.

    Article  CAS  Google Scholar 

  • Bird A . (2002). Genes Dev., 16, 6–21.

  • Bird A . (2003). Nat. Immunol., 4, 208–209.

  • Bird AP, Taggart M, Frommer M, Miller OJ and Macleod D . (1985). Cell, 40, 91–99.

    Article  CAS  Google Scholar 

  • Brandeis M, Frank D, Keshet I, Siegfried Z, Mendelsohn M, Nemes A, Temper V, Razin A and Cedar H . (1994). Nature, 371, 435–438.

    Article  CAS  Google Scholar 

  • Butler AJ and Ordhal CP . (1999). Mol. Cell Biol., 19, 296–306.

  • Clark SJ and Melki J . (2002). Oncogene, 21, 5380–5387.

    Article  CAS  Google Scholar 

  • Costello JF and Plass C . (2001). J. Med. Genet., 38, 285–303.

  • D'Amours D, Desnoyers S, D'Silva I and Poirier GG . (1999). Biochem. J., 342, 249–268.

    Article  CAS  Google Scholar 

  • Datta J, Ghoshal K, Sharma SM, Tajima S and Jacob ST . (2003). J. Cell. Biochem., 88, 855–864.

    Article  CAS  Google Scholar 

  • de Capoa A, Febbo Giovannelli FR, Niveleau A, Zardo G, Marenzi S and Caiafa P . (1999). FASEB J., 13, 89–93.

  • Fakan S, Leduc Y, Lamarre D, Brunet G and Poirier GG . (1988). Exp. Cell Res., 179, 517–526.

  • Feltus FA, Lee EK, Costello JF, Plass C and Vertino PM . (2003). Proc. Natl. Acad. Sci. USA, 21, 12253–12258.

  • Griesenbeck J, Ziegler M, Tomilin N, Schweiger M and Oei SL . (1999). FEBS Lett., 443, 20–24.

  • Hassa PO and Hottinger MO . (2002). Cell. Mol. Life Sci., 59, 1534–1553.

  • Jones PA and Takai D . (2001). Science, 293, 1068–1070.

    Article  CAS  Google Scholar 

  • Jones PA and Baylin SB . (2002). Nat. Genet., 3, 415–428.

  • Kraus WL and Lis JT . (2003). Cell, 113, 677–683.

    Article  CAS  Google Scholar 

  • Ku M-C, Stewart S and Hata A . (2003). Biochem. Biophys. Res. Commun., 311, 702–707.

  • Kun E, Kirsten E and Ordahl CP . (2002). J. Biol. Chem., 277, 39066–39069.

    Article  CAS  Google Scholar 

  • Laemmli UK . (1970). Nature, 227, 680.

    Article  CAS  Google Scholar 

  • Leonhardt H, Page AW, Weier H and Bestor TH . (1992). Cell, 71, 865–873.

    Article  CAS  Google Scholar 

  • Malanga M and Althaus FR . (1994). J. Biol. Chem., 269, 17961–17966.

  • Malanga M, Pleschke JM, Kleczkowska HE and Althaus FR . (1998). J. Biol. Chem., 273, 11839–11843.

    Article  CAS  Google Scholar 

  • Meisterernst M, Stelzer G and Roeder RG . (1997). Proc. Natl. Acad. Sci. USA, 94, 2261–2265.

  • Okano M, Bell DW, Haber DA and Li W . (1999). Cell, 99, 247–257.

    Article  CAS  Google Scholar 

  • Panzeter PL, Realini CA and Althaus FR . (1992). Biochemistry, 31, 1379–1385.

    Article  CAS  Google Scholar 

  • Panzeter PL, Zweifel B, Malanga M, Waser SH, Richard M and Althaus FR . (1993). J. Biol. Chem., 268, 17662–17664.

  • Pleschke JM, Kleczowska HE, Strohm M and Althaus FR . (2000). J. Biol. Chem., 275, 40974–40980.

    Article  CAS  Google Scholar 

  • Pradhan S, Bacolla A, Wells RD and Roberts RJ . (1999). J. Biol. Chem., 274, 33002–33010.

    Article  CAS  Google Scholar 

  • Robertson KD, Uzvolgyi E, Liang G, Talmadge C and Sumegi J . (1999). Nucleic Acids Res., 27, 2291–2298.

  • Rolli V, Ruf A, Augustin A, Schulz GE, Ménissier-de Murcia J and de Murcia G . (2000). From DNA Damage and Stress Signalling to Cell Death: Poly ADP-Ribosylation Reactions De Murcia G and Shall S (eds). Oxford University Press: New York, pp. 35–79.

    Google Scholar 

  • Schmitz AA, Pleschke JM, Kleczkowska HE, Althaus FR and Vergeres G . (1998). Biochemistry, 37, 9520–9527.

    Article  CAS  Google Scholar 

  • Takai D and Jones PA . (2002). Proc. Natl. Acad. Sci. USA, 99, 3740–3745.

  • Tulin A and Spradling A . (2003). Science, 299, 560–562.

    Article  CAS  Google Scholar 

  • Zardo G and Caiafa P . (1998). J. Biol. Chem., 273, 16517–16520.

    Article  CAS  Google Scholar 

  • Zardo G, D'Erme M, Reale A, Strom R, Perilli M and Caiafa P . (1997). Biochemistry, 36, 7937–7943.

    Article  CAS  Google Scholar 

  • Zardo G, Marenzi S, Perilli M and Caiafa P . (1999). FASEB J., 13, 1518–1522.

Download references

Acknowledgements

We thank Dr Sriharsa Pradhan (New Enagland Biolabs) for the generous gift of human recombinant DNMT1 and we greatly appreciate his experimental suggestions and his thoughtful support. This work was supported by Ministero Italiano dell'Università (COFIN, FIRB, 60%, Progetti di Ateneo), by AIRC project (P Caiafa), by Ministero della Salute (P Caiafa) and by Istituto Pasteur Cenci Bolognetti.

Author information

Authors and Affiliations

  1. Department of Cellular Biotechnologies and Haematology, University of Rome ‘La Sapienza’, 00161, Rome, Italy

    Anna Reale, Giovanna De Matteis, Giada Galleazzi, Michele Zampieri & Paola Caiafa

Authors
  1. Anna Reale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giovanna De Matteis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giada Galleazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michele Zampieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paola Caiafa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paola Caiafa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reale, A., Matteis, G., Galleazzi, G. et al. Modulation of DNMT1 activity by ADP-ribose polymers. Oncogene 24, 13–19 (2005). https://doi.org/10.1038/sj.onc.1208005

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208005

Keywords

This article is cited by

Search

Advanced search

Quick links