Nuclear structure in normal and Bloom syndrome cells.
Bloom syndrome (BS) is a rare cancer-predisposing disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. BLM, the protein altered in BS, is a RecQ DNA helicase. This report shows that BLM is found in the nucleus of normal human cells in the nuclear domain 10 or promyelocytic leukemia nuclear bodies. These structures are punctate depots of proteins disrupted upon viral infection and in certain human malignancies. BLM is found primarily in nuclear domain 10 except during S phase when it colocalizes with the Werner syndrome gene product, WRN, in the nucleolus. BLM colocalizes with a select subset of telomeres in normal cells and with large telomeric clusters seen in simian virus 40-transformed normal fibroblasts. During S phase, BS cells expel micronuclei containing sites of DNA synthesis. BLM is likely to be part of a DNA surveillance mechanism operating during S phase.
Yankiwski
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Laboratory of Molecular Genetics, New York Blood Center, 310 East 67th Street, New York, NY 10021, USA.
Marciniak
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Guarente
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Neff
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NF
D000251:Adenosine Triphosphatases / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D001816:Bloom Syndrome / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D002460:Cell Line; D002466:Cell Nucleolus / Q000201:enzymology / Q000648:ultrastructure; D002467:Cell Nucleus / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure*; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004265:DNA Helicases / Q000032:analysis*; D005090:Exodeoxyribonucleases; D005260:Female; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D053484:RecQ Helicases; D012016:Reference Values; D016196:S Phase; D016615:Telomere / Q000201:enzymology / Q000648:ultrastructure; D014898:Werner Syndrome / Q000201:enzymology; D000071657:Werner Syndrome Helicase
D005090:Exodeoxyribonucleases; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase