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Different DNA-PKcs functions in the repair of radiation-induced and spontaneous DSBs within interstitial telomeric sequences

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Abstract

Interstitial telomeric sequences (ITSs) in hamster cells are hot spots for spontaneous and induced chromosome aberrations (CAs). Most data on ITS instability to date have been obtained in DNA repair-proficient cells. The classical non-homologous end joining repair pathway (C-NHEJ), which is the principal double strand break (DSB) repair mechanism in mammalian cells, is thought to restore the morphologically correct chromosome structure. The production of CAs thus involves DNA-PKcs-independent repair pathways. In our current study, we investigated the participation of DNA-PKcs from the C-NHEJ pathway in the repair of spontaneous or radiation-induced DSBs in ITSs using wild-type and DNA-PKcs mutant Chinese hamster ovary cells. Our data demonstrate that DNA-PKcs stabilizes spontaneous DSBs within ITSs from the chromosome 9 long arm, leading to the formation of terminal deletions. In addition, we show that DNA-PKcs-dependent C-NHEJ is employed following radiation-induced DSBs in other ITSs and restores morphologically correct chromosomes, whereas DNA-PKcs independent mechanisms co-exist in DNA-PKcs proficient cells leading to an excess of CAs within ITSs.

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Acknowledgements

This work was supported by the European Community RISC-RAD contract—FI6R-CT-2003-508842. Deborah Revaud is supported by doctoral fellowships from the Commissariat à l'Energie Atomique and The Ligue. The authors thank Audrey Debronde for technical assistance and Janice Britton-Davidian for helpful discussions. PCR products of hamster chromosomes were a generous gift from Willem Rens (Cambridge University). CHO9 wild-type cells, mutant XR-C1B cells deficient for DNA-PKcs and the complemented XR-C1#8-1 hamster cell line were generously provided by M. Zdzienicka (Department of Radiation Genetics and Chemicals Mutagenesis, Leiden University-Medical Center, The Netherlands).

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The authors declare that the experiments comply with current laws in France.

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Laboratoire de Radiopathologie, Institut de Radiobiologie Cellulaire et Moléculaire CEA-DSV, INSERM UMR 967, Université Paris VII UMR 967, Université Paris XI UMR 967, 18 route du Panorama, 92265, Fontenay-aux-Roses, France

    Déborah Revaud, François D. Boussin & Chantal Desmaze

  2. CEA-DSV/iRCM/Laboratoire de Radiobiologie et d’Oncologie, Fontenay-aux-Roses, France

    Déborah Revaud, Laure Sabatier & Chantal Desmaze

  3. CEA-DSV/iRCM, Fontenay-aux-Roses, France

    Luis M. Martins

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  1. Déborah Revaud
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  2. Luis M. Martins
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Correspondence to Chantal Desmaze.

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Communicated by J. Karlseder

Laure Sabatier, Chantal Desmaze share leadership.

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Revaud, D., Martins, L.M., Boussin, F.D. et al. Different DNA-PKcs functions in the repair of radiation-induced and spontaneous DSBs within interstitial telomeric sequences. Chromosoma 120, 309–319 (2011). https://doi.org/10.1007/s00412-011-0313-1

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