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Blood, 2 July 2009, Vol. 114, No. 1, pp. 174-180. Prepublished online as a Blood First Edition Paper on May 7, 2009; DOI 10.1182/blood-2009-02-207811. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-02-207811v1 114/1/174    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 CrossRef Google Scholar Articles by Singh, T. R. Articles by Meetei, A. R. PubMed PubMed Citation Articles by Singh, T. R. Articles by Meetei, A. R. Related Collections Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS, IRON, AND ERYTHROPOIESIS Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M Thiyam Ramsing Singh1, Sietske T. Bakker2,3, Sheba Agarwal2, Michael Jansen1, Elke Grassman1, Barbara C. Godthelp4, Abdullah Mahmood Ali1, Chang-hu Du1, Martin A. Rooimans2, Qiang Fan1, Kebola Wahengbam1, Jurgen Steltenpool2, Paul R. Andreassen1, David A. Williams1, Hans Joenje2, Johan P. de Winter2, and Amom Ruhikanta Meetei1 1 Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, OH; 2 Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands; 3 Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; and 4 Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands FANCM is a component of the Fanconi anemia (FA) core complex and one FA patient (EUFA867) with biallelic mutations in FANCM has been described. Strikingly, we found that EUFA867 also carries biallelic mutations in FANCA. After correcting the FANCA defect in EUFA867 lymphoblasts, a "clean" FA-M cell line was generated. These cells were hypersensitive to mitomycin C, but unlike cells defective in other core complex members, FANCM–/– cells were proficient in monoubiquitinating FANCD2 and were sensitive to the topoisomerase inhibitor camptothecin, a feature shared only with the FA subtype D1 and N. In addition, FANCM–/– cells were sensitive to UV light. FANCM and a C-terminal deletion mutant rescued the cross-linker sensitivity of FANCM–/– cells, whereas a FANCM ATPase mutant did not. Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex–dependent and –independent manner. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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