Article
- The EMBO Journal (2005) 24, 1465 - 1476
- doi:10.1038/sj.emboj.7600622
Published online: 17 March 2005
Subject Category:
BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity
Jinhu Yin1,a, Alexandra Sobeck2,a, Chang Xu3,a, Amom Ruhikanta Meetei1, Maureen Hoatlin2, Lei Li3 and Weidong Wang1
- Laboratory of Genetics, National Institute on Aging, National Institute of Health, Baltimore, MD, USA
- Division of Molecular Medicine, Oregon Health & Science University, Portland, OR, USA
- Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Correspondence to:
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
aThese authors contributed equally to this work
Received 10 September 2004; Accepted 16 February 2005
Abstract
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.
Keywords:
- BLAP75,
- BLM,
- Bloom's syndrome,
- genomic instability,
- topoisomerase III
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