Central European Institute of Technology, Department of Genetics and Reproduction, Veterinary Research Institute, Brno, Czech Republic.
Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic.
Sci Rep. 2020 May 4;10(1):7455. doi: 10.1038/s41598-020-64418-1.
In several species, including Xenopus, mouse and human, two members of cyclin A family were identified. Cyclin A2, which is ubiquitously expressed in dividing cells and plays role in DNA replication, entry into mitosis and spindle assembly, and cyclin A1, whose function is less clear and which is expressed in spermatocytes, leukemia cells and in postmitotic multiciliated cells. Deletion of the gene showed that cyclin A1 is essential for male meiosis, but nonessential for female meiosis. Our results revealed, that the cyclin A1 is not only dispensable in oocytes, we show here that its expression is in fact undesirable in these cells. Our data demonstrate that the APC/C and proteasome in oocytes are unable to target sufficiently cyclin A1 before anaphase, which leads into anaphase arrest and direct inhibition of separase. The cyclin A1-induced cell cycle arrest is oocyte-specific and the presence of cyclin A1 in early embryos has no effect on cell cycle progression or chromosome division. Cyclin A1 is therefore not only an important cell cycle regulator with biased expression in germline, being essential for male and damaging for female meiosis, its persistent expression during anaphase in oocytes shows fundamental differences between APC/C function in oocytes and in early embryos.
在包括非洲爪蟾、小鼠和人类在内的几个物种中，已经鉴定出两种细胞周期蛋白 A 家族成员。细胞周期蛋白 A2 在有丝分裂细胞中广泛表达，在 DNA 复制、进入有丝分裂和纺锤体组装中发挥作用，而细胞周期蛋白 A1 的功能不太清楚，它在精母细胞、白血病细胞和有丝分裂后多纤毛细胞中表达。基因缺失表明细胞周期蛋白 A1 对于雄性减数分裂是必需的，但对于雌性减数分裂是非必需的。我们的研究结果表明，细胞周期蛋白 A1 在卵母细胞中不仅是可有可无的，我们在这里还表明，实际上在这些细胞中表达它是不可取的。我们的数据表明，在卵母细胞中，APC/C 和蛋白酶体在后期之前不能充分靶向细胞周期蛋白 A1，导致后期阻滞和分离酶的直接抑制。细胞周期蛋白 A1 诱导的细胞周期阻滞是卵母细胞特异性的，早期胚胎中细胞周期蛋白 A1 的存在对细胞周期进程或染色体分裂没有影响。因此，细胞周期蛋白 A1 不仅是一种重要的细胞周期调节剂，在生殖系中具有偏性表达，对于雄性减数分裂是必需的，对雌性减数分裂是有害的，它在卵母细胞后期的持续表达表明 APC/C 在卵母细胞和早期胚胎中的功能存在根本差异。
