Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes.
Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes.
复制标题
布卢姆综合征蛋白 (BLM) 与哺乳动物精母细胞减数分裂前期细胞核中的复制蛋白 A 共定位。
DOI：
10.1073/pnas.96.10.5622
复制
发表时间：
1999
影响因子：
11.1
通讯作者：
Ashley,T
中科院分区：
文献类型：
--
作者：
Walpita,D;Plug,AW;Neff,NF;German,J;Ashley,T
布卢姆综合征 (BS) 是一种罕见的人类常染色体隐性遗传疾病，其特征是严重的产前和产后生长缺陷、免疫缺陷、基因组不稳定以及易患多种肿瘤。 BS 体细胞中的基因组不稳定性表现为间隙和断裂、染色单体交换、染色体重排和位点特异性突变的高发生率。 BS 源于 BLM 的突变，BLM 是编码与 RecQ 解旋酶家族同源的蛋白质的基因。患有 BS 的男性是不育的；妇女的生育能力下降，生育期缩短。目前对小鼠精母细胞的免疫细胞学研究表明，BLM 蛋白首先作为减数分裂前期晚颧体中同源突触常染色体二价体的联会复合体 (SC) 上的离散病灶出现。 BLM 病灶在早期粗线期逐渐与突触常染色体轴分离，在粗线期中期不再可见。 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突触。然而，相对于复制蛋白 A，BLM 蛋白沿 SC 的出现存在时间延迟，这表明 BLM 是处理基因组 DNA 子集的后期步骤所必需的，该子集涉及早期减数分裂前期同源物间相互作用的建立。在粗线体后期和双线体中，BLM 更分散在核质中，特别是在与 SC 最密切相关的染色质上，表明 BLM 可能参与解决互锁，为后期 I 期间的同源染色体分离做准备。
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 inBLM, 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.