The SMC5/6 complex is involved in crucial processes during human spermatogenesis.

The SMC5/6 complex is involved in crucial processes during human spermatogenesis.
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DOI:
10.1095/biolreprod.114.118596
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发表时间:
2014-07
影响因子:
3.6
通讯作者:
Hamer G
Hamer G
中科院分区:
生物学2区
文献类型:
--
作者:
Verver DE;Langedijk NS;Jordan PW;Repping S;Hamer G

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基因组完整性对安全生殖至关重要。因此,在生殖细胞发育过程中,染色质的结构和动力学应该受到严格的调控。染色质的结构和功能在很大程度上是由染色体结构维持蛋白复合物(SMC)决定的,其中SMC 5/6最近被证明参与小鼠精子发生过程中的精原细胞分化和减数分裂。因此,我们研究了这种复合物在人类精子发生中的作用。我们发现SMC 6在人类睾丸中表达,并存在于Adark型和Apale型精原细胞、所有精母细胞和圆形精子细胞的一个子集中。在人类减数分裂过程中,SMC 5/6位于联会复合体(SC)、XY体和减数分裂中期的着丝粒上。然而,与小鼠精子发生相反,SMC 6不位于人类生精细胞的着丝粒周围异染色质,这表明SMC 5/6不仅在功能上存在细微但可能重要的差异,而且可能在重复的着丝粒周围区域维持基因组完整性方面也存在差异。尽管如此,我们的数据清楚地表明,SMC 5/6复合物,如在小鼠中所示,参与了人类精子发生过程中的许多关键过程,如精原细胞发育,突触染色体之间的SC,以及在粗线期未突触染色体上的DNA双链断裂修复。
Genome integrity is crucial for safe reproduction. Therefore, chromatin structure and dynamics should be tightly regulated during germ cell development. Chromatin structure and function are in large part determined by the structural maintenance of chromosomes (SMC) protein complexes, of which SMC5/6 recently has been shown to be involved in both spermatogonial differentiation and meiosis during mouse spermatogenesis. We therefore investigated the role of this complex in human spermatogenesis. We found SMC6 to be expressed in the human testis and present in a subset of type Adark and type Apale spermatogonia, all spermatocytes, and round spermatids. During human meiosis, SMC5/6 is located at the synaptonemal complex (SC), the XY body, and at the centromeres during meiotic metaphases. However, in contrast to mouse spermatogenesis, SMC6 is not located at pericentromeric heterochromatin in human spermatogenic cells, indicating subtle but perhaps important differences in not only SMC5/6 function but maybe also in maintenance of genomic integrity at the repetitive pericentromeric regions. Nonetheless, our data clearly indicate that the SMC5/6 complex, as shown in mice, is involved in numerous crucial processes during human spermatogenesis, such as in spermatogonial development, on the SC between synapsed chromosomes, and in DNA double-strand break repair on unsynapsed chromosomes during pachynema.
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