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Differential involvement of the hMRE11/hRAD50/NBS1 complex, BRCA1 and MLH1 in NF-κB activation by camptothecin and X-ray

Oncogene volume 22, pages 6090–6099 (2003)Cite this article

Abstract

Camptothecin (CPT) and X-ray (XR) generate double-strand breaks (DSB) that can be processed by homologous or nonhomologous recombination. We studied the participation of proteins involved in recombination pathways and cell cycle control in the signal transduction between DNA damage and NF-κB. Cells harbouring mutated NBS, hMRE11, BRCA1 or MLH1 were analysed. NBS- and hMRE11-deficient cells present a classical kinetic of NF-κB induction after camptothecin treatment. When DSB are generated by XR, NBS-deficient cells exhibit a delayed and strongly reduced level of NF-κB induction, whereas the hMRE11 mutated cells do not induce NF-κB at all. This indicates an important role of the hMRE11/hRAD50/NBS complex in the signal transduction initiated by XR. In HCC1937 cells that express a truncated version of BRCA1, XR induces a very rapid and transient NF-κB activation, whereas CPT leads to a delayed activation suggesting that BRCA1 modulates the transduction pathways in different manners after these two stresses. Finally, we found that a proficient MMR pathway is essential to the NF-κB activation after both CPT and XR. These results indicate that DSB originating from XR or CPT do not induce NF-κB in a unique way. MMR participates in both cascades, whereas the hMRE11/hRAD50/NBS trimer is specifically involved in the response elicited by XR.

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Acknowledgements

We are indebted to Dr M Zdzienicka (Leiden University, Netherlands) who kindly supplied us NBS-ILB1 cells and to Dr P Concannon (Virginia Mason Research Center, Seattle, USA) who sent us NBS-ILB1-6 cells. CWAT, ATLD2 and ATLD3 cells were a generous gift from Dr M Taylor (University of Birmingham, CRC Institute for Cancer Research, Birmingham, UK). We also thank Dr R Boland (UCSF, La Jolla, USA) for allowing us to use his corrected HCT116 3-6 cells. We thank Ch De Jesus for his assistance in this work. This work was supported by grants from the Belgian National Fund for Scientific Research (NFSR, Brussels, Belgium), from an IAP program (P5/12) and from a starting grant from the University of Liège. YH is a Research Scientist and JP is a Research Director, both supported by the NFSR. OJ is an assistant from the University of Liège.

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Authors and Affiliations

  1. Laboratory of Virology and Immunology, Institute of Pathology B23, University de Liège, Liège, B-4000, Belgium

    Yvette Habraken & Jacques Piette

  2. Laboratory of Human Histology, Immunology Centre, Institute of Anatomy L3, University of Liège, rue de Pitteurs 20, Liège, B-4020, Belgium

    Olivier Jolois

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  1. Yvette Habraken
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Correspondence to Yvette Habraken.

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Habraken, Y., Jolois, O. & Piette, J. Differential involvement of the hMRE11/hRAD50/NBS1 complex, BRCA1 and MLH1 in NF-κB activation by camptothecin and X-ray. Oncogene 22, 6090–6099 (2003). https://doi.org/10.1038/sj.onc.1206893

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