CDC6 regulates both G2/M transition and metaphase-to-anaphase transition during the first meiosis of mouse oocytes

Abstract

Cell division cycle protein CDC6 is essential for the initiation of DNA replication. CDC6 was recently shown to inhibit the microtubule-organizing activity of the centrosome. Here, we show that CDC6 is localized to the spindle from Pro-MI to MII stages of oocytes, and it plays important roles at two critical steps of oocyte meiotic maturation. CDC6 depletion facilitated the G2/M transition (GV breakdown, GVBD) through regulation of Cdh1 and cyclin B1 expression and CDK1 phosphorylation in a GVBD-inhibiting culture system containing milrinone.Furthermore, GVBD was significantly decreased after knockdown of cyclin B1 in CDC6-depleted oocytes, indicating that the effect of CDC6 loss on GVBD stimulation was mediated, at least in part, by raising cyclin B1. Knockdown of CDC6 also caused abnormal localization of γ -tubulin, resulting in defective spindles, misaligned chromosomes, cyclin B1 accumulation and spindle assembly checkpoint (SAC) activation, leading to significant Pro-MI/MI arrest and PB1 extrusion failure. These phenotypes were also confirmed by time-lapse live cell imaging analysis. The results indicate that CDC6 is indispensable for maintaining G2 arrest of meiosis and functions in G2/M checkpoint regulation in mouse oocytes. Moreover, CDC6 is also a key player regulating meiotic spindle assembly and metaphase-to-anaphase transition in meiotic oocytes.Summary statement：We show that CDC6 is indispensable for maintaining G2 arrest of mouse oocytes. Moreover, CDC6 is also a key player regulating meiotic spindle assembly and metaphase-to-anaphase transition in meiotic oocytes. resumption of meiosis in mouse oocytes. Hum Mol Genet. 21:2476. Althoff, F., Karess, R.E. and Lehner, C.F.( 2012). Spindle checkpoint-independent inhibition of mitotic chromosome segregation by Drosophila Mps1. Mol Biol Cell. 23:2275. Anger, M., Stein, P. and Schultz, R.M. (2005). CDC6 requirement for spindle formation during maturation of mouse oocytes. Biol Reprod. 72:188-194.

Research on the Influence of the Social Comparison Orientation on Online Compulsive Buying Tendency of Young People

“…After many scholars defined it, this paper believes that the definition can be regarded as "Under the network environment, consumers try to obtain the temporary relief of the negative feelings through addicted and unstopped online buying", based on Chinese Pronunciation General Hospital of Military Region. Currently, the existing research on predictive factors can be divided into the external stimulating factors [2] and the individual's psychological factors [3].…”