Expression and nuclear localization of BLM, a chromosome stability protein mutated in Bloom's syndrome, suggest a role in recombination during meiotic prophase.

Bloom's syndrome (BS) is a recessive human genetic disorder characterized by short stature, immunodeficiency and elevated risk of malignancy. BS cells have genomic instability and an increased frequency of sister chromatid exchange. The gene mutated in BS, BLM, encodes a 3'-5' helicase (BLM) with homology to bacterial recombination factor, RecQ. Human males homozygous for BLM mutations are infertile and heterozygous individuals display increased frequencies of structural chromosome abnormalities in their spermatozoa. Also, mutations in the Saccharomyces cerevisiae homolog of BLM, Sgs1, cause a delay in meiotic nuclear division and a reduction in spore viability. These observations suggest that BLM may play a role during meiosis. Our antibodies raised against the C terminus of the human protein specifically recognize both mouse and human BLM in western blots of cell lines and in successive developmental stages of spermatocytes, but fail to detect BLM protein in a cell line with a C-terminally truncated protein. BLM protein expression and location are detected by immunofluorescence and immunoelectron microscopy as discrete foci that are sparsely present on early meiotic prophase chromosome cores, later found abundantly on synapsed cores, frequently in combination with the recombinases RAD51 and DMC1, and eventually as pure BLM foci. The colocalization of RAD51/DMC1 with BLM and the statistically significant excess of BLM signals in the synapsed pseudoautosomal region of the X-Y chromosomes, which is a recombinational hot spot, provide indications that BLM protein may function in the meiotic recombination process.