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

Bloom's syndrome (BS) is a recessive human genetic disorder characterized b y short stature, immunodeficiency and elevated risk of malignancy, BS cells have genomic instability and an increased frequency of sister chromatid ex change. The gene mutated in BS, BLM, encodes a 3'-5' helicase (BLM) with ho mology 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, Al so, mutations in the Saccharomyces cerevisiae homolog of BLM, Sgs1, cause a delay in meiotic nuclear division and a reduction in spore viability. Thes e observations suggest that BLM may play a role during meiosis, Our antibod ies raised against the C terminus of the human protein specifically recogni ze both mouse and human BLM in western blots of cell lines and in successiv e developmental stages of spermatocytes, but fail to detect BLM protein in a cell line with a C-terminally truncated protein, BLM protein expression a nd location are detected by immunofluorescence and immunoelectron microscop y as discrete foci that are sparsely present on early meiotic prophase chro mosome cores, later found abundantly on synapsed cores, frequently in combi nation with the recombinases RAD51 and DMC1, and eventually as pure BLM foc i, The colocalization of RAD51/DMC1 with BLM and the statistically signific ant 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.