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ZNF198 protein, involved in rearrangement in myeloproliferative disease, forms complexes with the DNA repair-associated HHR6A/6B and RAD18 proteins

Oncogene volume 22, pages 3417–3423 (2003)Cite this article

Abstract

A highly specific t(8;13)(p11;q12) translocation has been consistently identified in bone marrow cells from patients with an atypical myeloproliferative disease that is associated with peripheral blood eosinophila and T- or B-cell leukemias. In all patients analysed to date, the translocation event results in a chimeric gene in which the atypical zinc-finger domain of ZNF198 is fused to the N-terminal end of the catalytic domain of the FGFR1 receptor tyrosine kinase. To understand more about the consequences of this rearrangement we have investigated the normal function of the ZNF198 gene. Using yeast two-hybrid analysis we identified HHR6 as a protein binding partner and confirmed this using immunoprecipitation studies. The ZNF198/FGFR1 fusion protein also binds to HHR6. We demonstrate here that the human RAD18 is also present in the ZNF198/HHR6 protein complex, although it does not coimmunoprecipitate with the fusion kinase. Cells expressing the fusion kinase gene show a marked increased sensitivity to UVB irradiation, suggesting that it acts in a dominant-negative way to affect DNA repair. These observations support the idea that ZNF198, through its interaction with HHR6 and RAD18, may be involved in the DNA repair process.

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Acknowledgements

This work was supported by Grant CA76167 from the National Institutes of Health and in part by the Roswell Park Cancer Center Support Grant (P30 CA 16056-26).

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Authors and Affiliations

  1. Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, 14263, NY, USA

    Padmaja Kunapuli, Ivan H Still & John K Cowell

  2. Department of Biomedical Engineering, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, 44195, OH, USA

    Robert Somerville

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  1. Padmaja Kunapuli
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Correspondence to John K Cowell.

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Kunapuli, P., Somerville, R., Still, I. et al. ZNF198 protein, involved in rearrangement in myeloproliferative disease, forms complexes with the DNA repair-associated HHR6A/6B and RAD18 proteins. Oncogene 22, 3417–3423 (2003). https://doi.org/10.1038/sj.onc.1206408

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