BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity

Jinhu Yin, Alexandra Sobeck, Chang Xu, Amom Ruhikanta Meetei, Maureen Hoatlin, Lei Li, Weidong Wang

Research output: Contribution to journalArticle

137 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1465-1476
Number of pages12
JournalEMBO Journal
Volume24
Issue number7
DOIs
StatePublished - Apr 6 2005

Keywords

  • BLAP75
  • BLM
  • Bloom's syndrome
  • Genomic instability
  • Topoisomerase IIIα

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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