Structure of the MLL CXXC domain–DNA complex and its functional role in MLL-AF9 leukemia

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作者
Tomasz Cierpicki
Laurie E Risner
Jolanta Grembecka
Stephen M Lukasik
Relja Popovic
Monika Omonkowska
David D Shultis
Nancy J Zeleznik-Le
John H Bushweller
机构
[1] University of Virginia,Department of Molecular Physiology and Biological Physics
[2] Molecular Biology Program,Department of Medicine
[3] Oncology Institute,Department of Chemistry
[4] Loyola University,undefined
[5] University of Virginia,undefined
[6] These authors contributed equally to this work. Present address: Department of Pathology,undefined
[7] University of Michigan,undefined
[8] Ann Arbor,undefined
[9] Michigan,undefined
[10] USA (T.C. and J.G.).,undefined
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MLL fusions are linked to leukemias and retain the CXXC domain, which binds unmethylated DNA. The NMR structure of CXXC–DNA now indicates the interactions underlying binding. Mutation of a key residue to a nonbinding form decreases proliferation caused by an MLL-AF9 fusion and leukemias induced by MLL-AF9 expression in mice.
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页码:62 / 68
页数:6
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