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| Subject Categories: Genome Stability & Dynamics |
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| The EMBO Journal
(2005) 24, 1465–1476, doi:10.1038/sj.emboj.7600622 Published online 17 March 2005 |
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| BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity |
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| Jinhu Yin1, 4, Alexandra Sobeck2, 4, Chang Xu3, 4, Amom Ruhikanta Meetei1, Maureen Hoatlin2, Lei Li3 and Weidong Wang1 |
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1 Laboratory of Genetics, National Institute on Aging, National Institute of Health, Baltimore, MD, USA 2 Division of Molecular Medicine, Oregon Health & Science University, Portland, OR, USA 3 Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA To whom correspondence should be addressed Weidong Wang, Laboratory of Genetics, National Institute on Aging/NIH, 333 Cassell Drive, TRIAD Building Rm 3000, Baltimore, MD 21224, USA. Tel.: +1 410 558 8334; Fax: +1 410 558 8331; E-mail: wangw@grc.nia.nih.gov 4 These authors contributed equally to this work Received 10 September 2004; Accepted 16 February 2005; Published online 17 March 2005. |
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| Abstract |
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| Bloom's syndrome (BS) is a rare human genetic disorder characterized by dwarfism, immunodeficiency, genomic instability and cancer predisposition. We have previously purified three complexes containing BLM, the helicase mutated in this disease. Here we demonstrate that BLAP75, a novel protein containing a putative OB-fold nucleic acid binding domain, is an integral component of BLM complexes, and is essential for their stability in vivo. Consistent with a role in BLM-mediated processes, BLAP75 colocalizes with BLM in subnuclear foci in response to DNA damage, and its depletion impairs the recruitment of BLM to these foci. Depletion of BLAP75 by siRNA also results in deficient phosphorylation of BLM during mitosis, as well as defective cell proliferation. Moreover, cells depleted of BLAP75 display an increased level of sister-chromatid exchange, similar to cells depleted of BLM by siRNA. Thus, BLAP75 is an essential component of the BLM-associated cellular machinery that maintains genome integrity. |
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Keywords: BLAP75, BLM, Bloom's syndrome, genomic instability, topoisomerase III |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSA new deal for Holliday junctions Nature Structural & Molecular Biology News and Views (01 Feb 2004) RESEARCHFunctional relationships of FANCC to homologous recombination, translesion synthesis, and BLM The EMBO Journal Article (26 Jan 2005) A novel ubiquitin ligase is deficient in Fanconi anemia Nature Genetics Letter (01 Oct 2003) The HRDC domain of BLM is required for the dissolution of double Holliday junctions The EMBO Journal Article (20 Jul 2005) |
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