SEARCH:   Advanced

Blood, 27 August 2009, Vol. 114, No. 9, pp. 1852-1858. Prepublished online as a Blood First Edition Paper on May 20, 2009; DOI 10.1182/blood-2008-08-175760. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-08-175760v1 114/9/1852    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 Google Scholar Articles by Wray, J. Articles by Hromas, R. PubMed PubMed Citation Articles by Wray, J. Articles by Hromas, R. Related Collections Myeloid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Metnase mediates chromosome decatenation in acute leukemia cells Justin Wray1, Elizabeth A. Williamson1, Sheema Sheema1, Suk-Hee Lee2, Edward Libby1, Cheryl L. Willman3, Jac A. Nickoloff4, and Robert Hromas1 1 Division of Hematology-Oncology, Cancer Research and Treatment Center, Department of Medicine, University of New Mexico Health Science Center, Albuquerque; 2 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis; 3 Department of Pathology, University of New Mexico Health Science Center, Albuquerque; and 4 Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque After DNA replication, sister chromatids must be untangled, or decatenated, before mitosis so that chromatids do not tear during anaphase. Topoisomerase II (Topo II) is the major decatenating enzyme. Topo II inhibitors prevent decatenation, causing cells to arrest during mitosis. Here we report that acute myeloid leukemia cells fail to arrest at the mitotic decatenation checkpoint, and their progression through this checkpoint is regulated by the DNA repair component Metnase (also termed SETMAR). Metnase contains a SET histone methylase and transposase nuclease domain, and is a component of the nonhomologous end-joining DNA double-strand break repair pathway. Metnase interacts with Topo II and enhances its decatenation activity. Here we show that multiple types of acute leukemia cells have an attenuated mitotic arrest when decatenation is inhibited and that in an acute myeloid leukemia (AML) cell line this is mediated by Metnase. Of further importance, Metnase permits continued proliferation of these AML cells even in the presence of the clinical Topo II inhibitor VP-16. In vitro, purified Metnase prevents VP-16 inhibition of Topo II decatenation of tangled DNA. Thus, Metnase expression levels may predict AML resistance to Topo II inhibitors, and Metnase is a potential therapeutic target for small molecule interference. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Decatenation: fixing your knots Duncan J. Clarke Blood 2009 114: 1721-1722. [Abstract] [Full Text] [PDF] This article has been cited by other articles: D. J. Clarke Decatenation: fixing your knots Blood, August 27, 2009; 114(9): 1721 - 1722. [Abstract] [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020