BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity.
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.
Yin
Jinhu
J
Laboratory of Genetics, National Institute on Aging, National Institute of Health, Baltimore, MD 21224, USA.
Sobeck
Alexandra
A
Xu
Chang
C
Meetei
Amom Ruhikanta
AR
Hoatlin
Maureen
M
Li
Lei
L
Wang
Weidong
W
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001816:Bloom Syndrome / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002457:Cell Extracts; D002458:Cell Fractionation; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D009841:Oligonucleotides; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics; D053484:RecQ Helicases; D017422:Sequence Analysis, DNA
D002352:Carrier Proteins; D002457:Cell Extracts; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D009841:Oligonucleotides; C501527:RMI1 protein, human; D034741:RNA, Small Interfering; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases