Chun-Jie Huang, Yi-Feng Yuan, Di Wu, Faheem Ahmed Khan, Xiao-Fei Jiao, Li-Jun Huo
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引用次数: 4
摘要
染色体上内聚力的维持和及时终止可确保染色体的准确分离,从而防止哺乳动物卵母细胞的非整倍体以及随后的染色体异常妊娠。Sororin是一种内聚力稳定剂,在有丝分裂过程中可拮抗类翼蛋白(Wapl)的反内聚力特性;然而,Sororin在哺乳动物卵母细胞减数分裂过程中的作用仍不清楚。在这里,我们发现索罗林是 DNA 损伤修复和染色体内聚力维持所必需的,因此也是小鼠卵母细胞减数分裂程序所必需的。Sororin在整个减数分裂过程中持续表达,并在生殖泡(GV)期/G2期时聚集在染色单体上。从生殖泡破裂(GVBD)到分裂后期的第二阶段,它都会定位在中心粒上。Sororin 失活会影响 GVBD 和第一次极体挤出(PBE)。此外,Sororin 失活还会诱发 DNA 损伤,表现为 GV 卵母细胞中的γH2AX 阳性病灶和 MII 卵母细胞中的染色质早分离。最后,我们的数据表明,PlK1 和 MPF 能使 Sororin 从染色体臂上解离,而不影响其着丝粒定位。我们的研究结果确定了Sororin在小鼠卵母细胞减数分裂成熟过程中的决定性作用,它有利于DNA损伤修复和染色体分离,从而维持基因组的稳定性并产生单倍体配子。
The cohesion stabilizer sororin favors DNA repair and chromosome segregation during mouse oocyte meiosis.
Maintenance and timely termination of cohesion on chromosomes ensures accurate chromosome segregation to guard against aneuploidy in mammalian oocytes and subsequent chromosomally abnormal pregnancies. Sororin, a cohesion stabilizer whose relevance in antagonizing the anti-cohesive property of Wings-apart like protein (Wapl), has been characterized in mitosis; however, the role of Sororin remains unclear during mammalian oocyte meiosis. Here, we show that Sororin is required for DNA damage repair and cohesion maintenance on chromosomes, and consequently, for mouse oocyte meiotic program. Sororin is constantly expressed throughout meiosis and accumulates on chromatins at germinal vesicle (GV) stage/G2 phase. It localizes onto centromeres from germinal vesicle breakdown (GVBD) to metaphase II stage. Inactivation of Sororin compromises the GVBD and first polar body extrusion (PBE). Furthermore, Sororin inactivation induces DNA damage indicated by positive γH2AX foci in GV oocytes and precocious chromatin segregation in MII oocytes. Finally, our data indicate that PlK1 and MPF dissociate Sororin from chromosome arms without affecting its centromeric localization. Our results define Sororin as a determinant during mouse oocyte meiotic maturation by favoring DNA damage repair and chromosome separation, and thereby, maintaining the genome stability and generating haploid gametes.
期刊介绍:
The South African Archaeological Bulletin - the longest established archaeological journal in sub-Saharan Africa, it contains the cutting edge of research on southern Africa. Appearing twice a year, it includes current research, notes by readers and book reviews.