Nuclear structure in normal and Bloom syndrome cells

Bloom syndrome (BS) is a rare cancer-predisposing disorder in which the cel ls of affected persons have a high frequency of somatic mutation and genomi c 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 structur es are punctate depots of proteins disrupted upon viral infection and in ce rtain human malignancies. BLM is found primarily in nuclear domain 10 excep t during S phase when it colocalizes with the Werner syndrome gene product, WRN, in the nucleolus. BLM colocalizes with a select subset of telomeres i n normal cells and with large telomeric clusters seen in simian virus 40-tr ansformed normal fibroblasts. During S phase, BS cells expel micronuclei co ntaining sites of DNA synthesis. BLM is likely to be part of a DNA surveill ance mechanism operating during S phase.