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Blood, 5 March 2009, Vol. 113, No. 10, pp. 2181-2190. Prepublished online as a Blood First Edition Paper on December 24, 2008; DOI 10.1182/blood-2008-05-154294. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-05-154294v1 113/10/2181    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 Collins, N. B. Articles by Kupfer, G. M. Search for Related Content PubMed PubMed Citation Articles by Collins, N. B. Articles by Kupfer, G. M. Related Collections Hematopoiesis and Stem Cells Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS ATR-dependent phosphorylation of FANCA on serine 1449 after DNA damage is important for FA pathway function Natalie B. Collins1, James B. Wilson2, Thomas Bush3, Andrei Thomashevski3, Kate J. Roberts2, Nigel J. Jones2, and Gary M. Kupfer3 1 Department of Microbiology, University of Virginia School of Medicine, Charlottesville; 2 School of Biological Sciences, University of Liverpool, Liverpool, United Kingdom; and 3 Division of Pediatric Hematology-Oncology, Yale University School of Medicine, New Haven, CT Previous work has shown several proteins defective in Fanconi anemia (FA) are phosphorylated in a functionally critical manner. FANCA is phosphorylated after DNA damage and localized to chromatin, but the site and significance of this phosphorylation are unknown. Mass spectrometry of FANCA revealed one phosphopeptide, phosphorylated on serine 1449. Serine 1449 phosphorylation was induced after DNA damage but not during S phase, in contrast to other posttranslational modifications of FA proteins. Furthermore, the S1449A mutant failed to completely correct a variety of FA-associated phenotypes. The DNA damage response is coordinated by phosphorylation events initiated by apical kinases ATM (ataxia telangectasia mutated) and ATR (ATM and Rad3-related), and ATR is essential for proper FA pathway function. Serine 1449 is in a consensus ATM/ATR site, phosphorylation in vivo is dependent on ATR, and ATR phosphorylated FANCA on serine 1449 in vitro. Phosphorylation of FANCA on serine 1449 is a DNA damage–specific event that is downstream of ATR and is functionally important in the FA pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Zhi, J. B. Wilson, X. Chen, D. S. Krause, Y. Xiao, N. J. Jones, and G. M. Kupfer Fanconi Anemia Complementation Group FANCD2 Protein Serine 331 Phosphorylation Is Important for Fanconi Anemia Pathway Function and BRCA2 Interaction Cancer Res., November 15, 2009; 69(22): 8775 - 8783. [Abstract] [Full Text] [PDF] J. Du, L. Chen, and J. Shen Identification of FANCA as a protein interacting with centromere-associated protein E Acta Biochim Biophys Sin, October 1, 2009; 41(10): 816 - 821. [Abstract] [Full Text] [PDF]

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