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Novel evidences for a tumor suppressor role of Rev3, the catalytic subunit of Pol ζ

Oncogene volume 27, pages 6093–6101 (2008)Cite this article

Abstract

Cell cycle checkpoints and DNA repair act in concert to ensure DNA integrity during perturbation of normal replication or in response to genotoxic agents. Deficiencies in these protective mechanisms can lead to cellular transformation and ultimately tumorigenesis. Here we focused on Rev3, the catalytic subunit of the low-fidelity DNA repair polymerase ζ. Rev3 is believed to play a role in double-strand break (DSB)-induced DNA repair by homologous recombination. In line with this hypothesis, we show the accumulation of chromatin-bound Rev3 protein in late S–G2 of untreated cells and in response to clastogenic DNA damage as well as an γ-H2AX accumulation in Rev3-depleted cells. Moreover, serine 995 of Rev3 is in vitro phosphorylated by the DSB-inducible checkpoint kinase, Chk2. Our data also disclose a significant reduction of rev3 gene expression in 74 colon carcinomas when compared to the normal adjacent tissues. This reduced expression is independent of the carcinoma stages, suggesting that the downregulation of rev3 might have occurred early during tumorigenesis.

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Acknowledgements

We gratefully thank Professor CW Lawrence for providing Rev3 cDNA and Dr C Jorgensen for gift of human mesenchymal stem cells. We also greatly thank R Guimbaud and K Gordien (Inserm/CHU Purpan, Toulouse) for collection and annotation of the tumors, as well as JM Maoret from the plateforme de ‘Génomique et Biologie Moléculaire’, IFR31 Toulouse for his technical help on the 7900HT fast real-time PCR systems. This work was supported by the Canceropole Grand Sud Ouest grant 2003-2006 and the Association pour la Recherche sur le Cancer.

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Authors and Affiliations

  1. Centre Régional de Cancérologie de Montpellier (INSERM-Université de Montpellier I Unité 868) Identité et Plasticité Tumorale, CRCM Val d’Aurelle-Lamarque, Montpellier cedex 5, France

    J-M Brondello, C Rodriguez & J Piette

  2. INSERM U844 Hôpital Saint Eloi Bâtiment INM BP74103, Montpellier, France

    J-M Brondello

  3. IPBS, CNRS UMR 5089, Toulouse, France

    M J Pillaire & C Cazaux

  4. Département d’Epidémiologie et de Santé Publique, Unité de Recherche Clinique, Service Hospitalier d’Epidémiologie, CHU de Toulouse, INSERM U558-Université Toulouse III, Faculté de Médecine, Toulouse, France

    P-A Gourraud

  5. Federation of Digestive Cancerology and Department of Anatomo-pathology, INSERM U563, Centre of Physiopathology of Toulouse-Purpan, Paul Sabatier University, Toulouse, France

    J Selves

  6. Institut de Génétique Moléculaire de Montpellier CNRS-UMR5535 1919 Route de Mende, Montpellier, France

    J Piette

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  1. J-M Brondello
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Correspondence to J-M Brondello.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Brondello, JM., Pillaire, M., Rodriguez, C. et al. Novel evidences for a tumor suppressor role of Rev3, the catalytic subunit of Pol ζ. Oncogene 27, 6093–6101 (2008). https://doi.org/10.1038/onc.2008.212

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