Walpita D, Plug A W, Neff N F, German J, Ashley T
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5622-7. doi: 10.1073/pnas.96.10.5622.
Bloom's syndrome (BS) is a rare autosomal recessive disorder of humans characterized by severe pre- and postnatal growth deficiency, immunodeficiency, genomic instability, and a predisposition to a wide variety of neoplasms. The genomic instability is evidenced in BS somatic cells as a high incidence of gaps and breaks, chromatid exchanges, chromosome rearrangements, and locus-specific mutations. BS arises from a mutation in BLM, a gene encoding a protein with homology to the RecQ helicase family. Men with BS are sterile; women have reduced fertility and a shortened reproductive span. The current immunocytological study on mouse spermatocytes shows that the BLM protein is first evident as discrete foci along the synaptonemal complexes (SCs) of homologously synapsed autosomal bivalents in late zygonema of meiotic prophase. BLM foci progressively dissociate from the synapsed autosomal axes during early pachynema and are no longer seen in mid-pachynema. BLM colocalizes with the single-stranded DNA binding replication protein A, which has been shown to be involved in meiotic synapsis. However, there is a temporal delay in the appearance of BLM protein along the SCs relative to replication protein A, suggesting that BLM is required for a late step in processing of a subset of genomic DNA involved in establishment of interhomologue interactions in early meiotic prophase. In late pachynema and into diplonema, BLM is more dispersed in the nucleoplasm, especially over the chromatin most intimately associated with the SCs, suggesting a possible involvement of BLM in resolution of interlocks in preparation for homologous chromosome disjunction during anaphase I.
布卢姆综合征（BS）是一种罕见的人类常染色体隐性疾病，其特征为严重的产前和产后生长发育迟缓、免疫缺陷、基因组不稳定，以及易患多种肿瘤。基因组不稳定在BS体细胞中表现为高频率的缺口和断裂、染色单体交换、染色体重排以及基因座特异性突变。BS是由BLM基因突变引起的，BLM基因编码一种与RecQ解旋酶家族具有同源性的蛋白质。患有BS的男性不育；女性生育能力下降，生殖期缩短。目前对小鼠精母细胞的免疫细胞研究表明，BLM蛋白最初表现为减数分裂前期双线期同源配对的常染色体二价体的联会复合体（SCs）上的离散焦点。在粗线期早期，BLM焦点逐渐从配对的常染色体轴上解离，在粗线期中段不再可见。BLM与单链DNA结合复制蛋白A共定位，该蛋白已被证明参与减数分裂联会。然而，相对于复制蛋白A，BLM蛋白在SCs上出现的时间有延迟，这表明BLM是减数分裂前期早期建立同源物间相互作用所涉及的一部分基因组DNA加工后期步骤所必需的。在粗线期末期和双线期，BLM在核质中分布更分散，特别是在与SCs最紧密相关的染色质上，这表明BLM可能参与解开互锁，为减数第一次分裂后期同源染色体分离做准备。
