Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Mol Reprod Dev. 2009 Nov;76(11):1094-105. doi: 10.1002/mrd.21075.
The elevated incidence of aneuploidy in human oocytes warrants study of the molecular mechanisms regulating proper chromosome segregation. The Aurora kinases are a well-conserved family of serine/threonine kinases that are involved in proper chromosome segregation during mitosis and meiosis. Here we report the expression and localization of all three Aurora kinase homologs, AURKA, AURKB, and AURKC, during meiotic maturation of mouse oocytes. AURKA, the most abundantly expressed homolog, localizes to the spindle poles during meiosis I (MI) and meiosis II (MII), whereas AURKB is concentrated at kinetochores, specifically at metaphase of MI (Met I). The germ cell-specific homolog, AURKC, is found along the entire length of chromosomes during both meiotic divisions. Maturing oocytes in the presence of the small molecule pan-Aurora kinase inhibitor, ZM447439 results in defects in meiotic progression and chromosome alignment at both Met I and Met II. Over-expression of AURKB, but not AURKA or AURKC, rescues the chromosome alignment defect suggesting that AURKB is the primary Aurora kinase responsible for regulating chromosome dynamics during meiosis in mouse oocytes.
人类卵母细胞中存在着较高的非整倍体发生率,这就需要研究调节正确染色体分离的分子机制。Aurora 激酶是一类高度保守的丝氨酸/苏氨酸激酶家族,在有丝分裂和减数分裂过程中参与正确的染色体分离。在这里,我们报告了在小鼠卵母细胞减数成熟过程中三种 Aurora 激酶同源物(AURKA、AURKB 和 AURKC)的表达和定位。AURKA 是表达最丰富的同源物,在减数分裂 I(MI)和减数分裂 II(MII)期间定位于纺锤体极,而 AURKB 集中在动粒上,特别是在 MI 的中期(Met I)。生殖细胞特异性同源物 AURKC 在两个减数分裂过程中都沿着染色体的全长存在。在小分子泛 Aurora 激酶抑制剂 ZM447439 的存在下,成熟卵母细胞的减数分裂进程和 MI 和 Met II 中的染色体排列都会出现缺陷。AURKB 的过表达,但不是 AURKA 或 AURKC 的过表达,可以挽救染色体排列缺陷,表明 AURKB 是在小鼠卵母细胞减数分裂过程中调节染色体动力学的主要 Aurora 激酶。