Article abstract
Nature Cell Biology 4, 913 - 920 (2002)
Published online: 25 November 2002 | doi:10.1038/ncb879
Interaction of FANCD2 and NBS1 in the DNA damage response
Koji Nakanishi1, Toshiyasu Taniguchi1, Velvizhi Ranganathan2, Helen V. New3, Lisa A. Moreau1, Maria Stotsky1, Christopher G. Mathew4, Michael B. Kastan5, David T. Weaver2 & Alan D. D'Andrea1
Abstract
Fanconi anaemia (FA) and Nijmegen breakage syndrome (NBS) are autosomal recessive chromosome instability syndromes with distinct clinical phenotypes. Cells from individuals affected with FA are hypersensitive to mitomycin C (MMC), and cells from those with NBS are hypersensitive to ionizing radiation. Here we report that both NBS cell lines and individuals with NBS are hypersensitive to MMC, indicating that there may be functional linkage between FA and NBS. In wild-type cells, MMC activates the colocalization of the FA subtype D2 protein (FANCD2) and NBS1 protein in subnuclear foci. Ionizing radiation activates the ataxia telangiectasia kinase (ATM)-dependent and NBS1-dependent phosphorylation of FANCD2, resulting in an S-phase checkpoint. NBS1 and FANCD2 therefore cooperate in two distinct cellular functions, one involved in the DNA crosslink response and one involved in the S-phase checkpoint response.
- Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
- Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
- Department of Haematology, Great Ormond Street Hospital, Great Ormond Street, London, WC1N 3JH, UK
- Division of Medical and Molecular Genetics, Guy's, King's, and St Thomas School of Medicine, 8th Floor, Guy's Tower, SE1 9RT, London, UK
- Department of Hematology-Oncology, St. Jude Children's Research Hospital, 323 North Lauderdale Street, Memphis, TN 38105, USA
Correspondence to: Alan D. D'Andrea1 e-mail: alan_dandrea@dfci.harvard.edu
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