生物
布鲁姆综合征
前期
遗传学
雷达51
减数分裂
基因组不稳定性
分子生物学
同源重组
基因
解旋酶
DNA
DNA损伤
核糖核酸
作者
Peter B. Møens,Raimundo Freire,Madalina Tarsounas,Barbara Spyropoulos,Stephen P. Jackson
标识
DOI:10.1242/jcs.113.4.663
摘要
ABSTRACT 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 BLMmutations are infertile and heterozygous individuals display increased frequencies of structural chromosome abnormalities in their spermatozoa. Also, mutations in the Saccharomyces cerevisiaehomolog 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.
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