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.

  • Short Communication
  • Published:

The nucleoporin 153, a novel factor in double-strand break repair and DNA damage response

Oncogene volume 31, pages 4803–4809 (2012)Cite this article

Subjects

Abstract

DNA repair is essential in maintaining genome integrity and defects in different steps of the process have been linked to cancer and aging. It is a long lasting question how DNA repair is spatially and temporarily organized in the highly compartmentalized nucleus and whether the diverse nuclear compartments regulate differently the efficiency of repair. Increasing evidence suggest the involvement of nuclear pore complexes in repair of double-strand breaks (DSBs) in yeast. Here, we show that the human nucleoporin 153 (NUP153) has a role in repair of DSBs and in the activation of DNA damage checkpoints. We explore the mechanism of action of NUP153 and we propose its potential as a novel therapeutic target in cancers.

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
Figure 4

Similar content being viewed by others

References

  1. Jackson SP, Bartek J . The DNA-damage response in human biology and disease. Nature 2009; 461: 1071–1078.

    Article  CAS  Google Scholar 

  2. Misteli T, Soutoglou E . The emerging role of nuclear architecture in DNA repair and genome maintenance. Nat Rev Mol Cell Biol 2009; 10: 243–254.

    Article  CAS  Google Scholar 

  3. Bartek J, Lukas J . DNA damage checkpoints: from initiation to recovery or adaptation. Curr Opin Cell Biol 2007; 19: 238–245.

    Article  CAS  Google Scholar 

  4. Lisby M, Mortensen UH, Rothstein R . Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre. Nat Cell Biol 2003; 5: 572–577.

    Article  CAS  Google Scholar 

  5. Nagai S, Dubrana K, Tsai-Pflugfelder M, Davidson MB, Roberts TM, Brown GW et al. Science 2008; 322: 597–602.

    Article  CAS  Google Scholar 

  6. Oza P, Jaspersen SL, Miele A, Dekker J, Peterson CL . Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. Genes & Development 2009; 23: 912–927.

    Article  CAS  Google Scholar 

  7. Loeillet S, Palancade Bt, Cartron M, Thierry As, Richard G-F, Dujon B et al. Genetic network interactions among replication, repair and nuclear pore deficiencies in yeast. DNA Repair 2005; 4: 459–468.

    Article  CAS  Google Scholar 

  8. Bermejo R, Capra T, Jossen R, Colosio A, Frattini C, Carotenuto W et al. The Replication Checkpoint Protects Fork Stability by Releasing Transcribed Genes from Nuclear Pores. Cell 2011; 146: 233–246.

    Article  CAS  Google Scholar 

  9. Soutoglou E, Dorn JF, Sengupta K, Jasin M, Nussenzweig A, Ried T et al. Nat Cell Biol 2007; 9: 675–682.

    Article  CAS  Google Scholar 

  10. Weinstock DM, Nakanishi K, Helgadottir HR, Jasin M . Assaying Double-Strand Break Repair Pathway Choice in Mammalian Cells Using a Targeted Endonuclease or the RAG Recombinase. Methods Enzymol 2006; 409: 524–540.

    Article  CAS  Google Scholar 

  11. Miller KM, Tjeertes JV, Coates J, Legube G, Polo SE, Britton S et al. Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. Nat Struct Mol Biol 2010; 17: 1144–1151.

    Article  CAS  Google Scholar 

  12. Rass E, Grabarz A, Plo I, Gautier J, Bertrand P, Lopez BS . Role of Mre11 in chromosomal nonhomologous end joining in mammalian cells. Nat Struct Mol Biol 2009; 16: 819–824.

    Article  CAS  Google Scholar 

  13. Guirouilh-Barbat Je, Huck S, Bertrand P, Pirzio L, Desmaze C, Sabatier L et al. Molecular Cell 2004; 14: 611–623.

    Article  CAS  Google Scholar 

  14. Xie A, Hartlerode A, Stucki M, Odate S, Puget N, Kwok A et al. Molecular Cell 2007; 28: 1045–1057.

    Article  CAS  Google Scholar 

  15. Yoshida M, Horinouchi S . Trichostatin and Leptomycin: Inhibition of Histone Deacetylation and Signal-Dependent Nuclear Export. Ann N Y Acad Sci 1999; 886: 23–35.

    Article  CAS  Google Scholar 

  16. Walther TC, Fornerod M, Pickersgill H, Goldberg M, Allen TD, Mattaj IW . The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins. EMBO J 2001; 20: 5703–5714.

    Article  CAS  Google Scholar 

  17. Moudry P, Lukas C, Macurek L, Neumann B, Heriche J-K, Pepperkok R et al. Nucleoporin NUP153 guards genome integrity by promoting nuclear import of 53BP1. Cell Death Differ 2011 (e-pub ahead of print 11 November 2011; doi:10.1038/cdd.2011.150).

    Article  Google Scholar 

  18. Bunting SF, Callén E, Wong N, Chen H-T, Polato F, Gunn A et al. 53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks. Cell 2010; 141: 243–254.

    Article  CAS  Google Scholar 

  19. Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der Gulden H et al. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat Struct Mol Biol 2010; 17: 688–695.

    Article  CAS  Google Scholar 

  20. Mochan TA, Venere M, DiTullio RA, Halazonetis TD . 53BP1 and NFBD1/MDC1-Nbs1 Function in Parallel Interacting Pathways Activating Ataxia-Telangiectasia Mutated (ATM) in Response to DNA Damage. Cancer Res 2003; 63: 8586–8591.

    CAS  Google Scholar 

  21. Lee J-H, Goodarzi AA, Jeggo PA, Paull TT . 53BP1 promotes ATM activity through direct interactions with the MRN complex. EMBO J 2010; 29: 574–585.

    Article  CAS  Google Scholar 

  22. Noon AT, Shibata A, Rief N, Lobrich M, Stewart GS, Jeggo PA et al. 53BP1-dependent robust localized KAP-1 phosphorylation is essential for heterochromatic DNA double-strand break repair. Nat Cell Biol 2010; 12: 177–184.

    Article  CAS  Google Scholar 

  23. Minter-Dykhouse K, Ward I, Huen MSY, Chen J, Lou Z . Distinct versus overlapping functions of MDC1 and 53BP1 in DNA damage response and tumorigenesis. J Cell Biol 2008; 181: 727–735.

    Article  CAS  Google Scholar 

  24. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, Hurov KE, Luo J et al. ATM and ATR Substrate Analysis Reveals Extensive Protein Networks Responsive to DNA Damage. Science 2007; 316: 1160–1166.

    Article  CAS  Google Scholar 

  25. Palancade B, Liu X, Garcia-Rubio M, Aguilera As, Zhao X, Doye Vr . Nucleoporins Prevent DNA Damage Accumulation by Modulating Ulp1-dependent Sumoylation Processes. Mol Biol Cell 2007; 18: 2912–2923.

    Article  CAS  Google Scholar 

  26. Soutoglou E, Misteli T . Activation of the cellular DNA damage response in the absence of DNA lesions. Science 2008; 320: 1507–1510.

    Article  CAS  Google Scholar 

  27. Reddy KL, Singh H . Using molecular tethering to analyze the role of nuclear compartmentalization in the regulation of mammalian gene activity. Methods 2008; 45: 242–251.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Amélie Weiss, Laure Froidevaux and Audrey Furst for excellent technical assistance. The GFP-NUP153 vector was provided by Ian Ellenberg (EMBL, Heidelberg). We are grateful to Zita Nagy and Tibor Pankotai for critical reading of the manuscript. C.L. is supported by the Région Alsace. The research in E.S. lab is funded by CNRS, ANR, INCA and HFSP. We thank the imaging center of IGBMC and particularly Marc Koch for the help with the multi photon laser experiments.

Author information

Authors and Affiliations

  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), UMR 7104 CNRS, CU de Strasbourg, France

    C Lemaître, A Kalousi, A-S Hoffbeck & E Soutoglou

  2. High Throughput Screening Facility, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), UMR 7104 CNRS, CU de Strasbourg, France

    B Fischer & L Brino

  3. CNRS, UMR217, Institute for Cellular and Molecular Radiobiology, Fontenay aux Roses, France

    J Guirouilh-Barbat, D Genet, P Betrand & B Lopez

  4. Department of Genetics, The Institute of Life Sciences, The Hebrew University, Jerusalem, Israel

    O D Shahar & M Goldberg

Authors
  1. C Lemaître
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Kalousi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A-S Hoffbeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Guirouilh-Barbat
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. O D Shahar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D Genet
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M Goldberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P Betrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. B Lopez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. L Brino
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. E Soutoglou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E Soutoglou.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Oncogene website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lemaître, C., Fischer, B., Kalousi, A. et al. The nucleoporin 153, a novel factor in double-strand break repair and DNA damage response. Oncogene 31, 4803–4809 (2012). https://doi.org/10.1038/onc.2011.638

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2011.638

Keywords

This article is cited by

Search

Advanced search

Quick links