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Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2002-10-3207. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3207v1 102/7/2632    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Canitrot, Y. Articles by Skorski, T. Search for Related Content PubMed PubMed Citation Articles by Canitrot, Y. Articles by Skorski, T. Related Collections Oncogenes and Tumor Suppressors Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 October 2003, Vol. 102, No. 7, pp. 2632-2637 NEOPLASIA p210 BCR/ABL kinase regulates nucleotide excision repair (NER) and resistance to UV radiation Yvan Canitrot, Rafal Falinski, Thierry Louat, Guy Laurent, Christophe Cazaux, Jean-Sébastien Hoffmann, Dominique Lautier, and Tomasz Skorski From the Genetic Instability and Cancer, Institut de Pharmacologie et Biologie Structurale, Toulouse, France; Center for Biotechnology, Temple University, Philadelphia, PA; Institut National de la Santé et de la Recherche Médicale (INSERM) U563, Institut Claudius Regaud, Toulouse, France; and Service d'Hematologie, Centre Hospitalièr Universitaire Purpan, Toulouse, France. Both clinical and experimental evidence illustrate that p190 and p210 BCR/ABL oncogenic tyrosine kinases induce resistance to DNA damage and confer an intrinsic genetic instability. Here, we investigated whether BCR/ABL expression could modulate nucleotide excision repair (NER). We found that ectopic expression of p210 BCR/ABL in murine lymphoid BaF3 cell line inhibited NER activity in vitro, promoting hypersensitivity of these cells to ultraviolet (UV) treatment and facilitating a mutator phenotype. However, expression of p210 BCR/ABL in human and murine myeloid cell lines and primary bone marrow cells resulted in the increased NER activity and resistance to UV irradiation. The ABL tyrosine kinase inhibitor STI571 reversed these effects, showing that p210 BCR/ABL tyrosine kinase activity is responsible for deregulation of NER. Hypoactivity of NER in p210 BCR/ABL-positive lymphoid cells was accompanied by the decreased interaction between proliferating cell nuclear antigen (PCNA) and xeroderma pigmentosum group B (XPB); conversely, this interaction was enhanced in p210 BCR/ABL-positive myeloid cells. p190 BCR/ABL did not affect NER in lymphoid and myeloid cells. In summary, our study suggests that p210 BCR/ABL reduced NER activity in lymphoid cells, leading to hypersensitivity to UV and mutagenesis. In contrast, p210 BCR/ABL expression in myeloid cells facilitated NER and induced resistance to UV. (Blood. 2003;102:2632-2637) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Stoklosa, T. Poplawski, M. Koptyra, M. Nieborowska-Skorska, G. Basak, A. Slupianek, M. Rayevskaya, I. Seferynska, L. Herrera, J. Blasiak, et al. 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