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CDC6 regulates both G2/M transition and metaphase‐to‐anaphase transition during the first meiosis of mouse oocytes
Author(s) -
Yi ZiYun,
Meng TieGang,
Ma XueShan,
Li Jian,
Zhang ChunHui,
Ouyang YingChun,
Schatten Heide,
Qiao Jie,
Sun QingYuan,
Qian WeiPing
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29469
Subject(s) - microbiology and biotechnology , cyclin b1 , germinal vesicle , spindle checkpoint , centrosome , cyclin b , cyclin dependent kinase 1 , metaphase , multipolar spindles , anaphase , cell cycle checkpoint , biology , meiosis , g2 m dna damage checkpoint , chemistry , oocyte , cell cycle , cyclin , spindle apparatus , genetics , cell division , chromosome , cell , embryo , gene
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‐metaphase I (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 (germinal vesicle breakdown [GVBD]) through regulation of Cdh1 and cyclin B1 expression and CDK1 (CDC2) 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.