title: Checkpoint kinase 1 is essential for meiotic cell cycle regulation in mouse oocytes.
abstract: Checkpoint kinase 1 (Chk1) plays key roles in all currently defined cell cycle checkpoints, but its functions in mouse oocyte meiosis remain unclear. In this study, we report the expression, localization and functions of Chk1 in mouse oocyte meiosis. Chk1 was expressed from germinal vesicle (GV) to metaphase II (MII) stages and localized to the spindle from pro-metaphase I (pro-MI) to MII stages in mouse oocytes. Chk1 depletion facilitated the G 2/M transition while Chk1 overexpression inhibited the G 2/M transition as indicated by germinal vesicle breakdown (GVBD), through regulation of Cdh1 and Cyclin B1. Chk1 depletion did not affect meiotic cell cycle progression after GVBD, but its overexpression after GVBD activated the spindle assembly checkpoint and prevented homologous chromosome segregation, thus arresting oocytes at pro-MI or metaphase I (MI) stages. These results suggest that Chk1 is indispensable for prophase I arrest and functions in G 2/M checkpoint regulation in meiotic oocytes. Moreover, Chk1 overexpression affects meiotic spindle assembly checkpoint regulation and thus chromosome segregation.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology; Chinese Academy of Sciences, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Shi-Bin
authors.initials: SB
authors.lastname: Chao
authors.forename: Zhen-Bo
authors.initials: ZB
authors.lastname: Wang
authors.forename: Shu-Tao
authors.initials: ST
authors.lastname: Qi
authors.forename: Xiu-Lan
authors.initials: XL
authors.lastname: Zhu
authors.forename: Shang-Wu
authors.initials: SW
authors.lastname: Yang
authors.forename: Cai-Rong
authors.initials: CR
authors.lastname: Yang
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Zhang
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Ouyang
authors.forename: Yi
authors.initials: Y
authors.lastname: Hou
authors.forename: Heide
authors.initials: H
authors.lastname: Schatten
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Sun
mesh_terms: D000818:Animals; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D000071877:Checkpoint Kinase 1; D020090:Chromosome Segregation; D056744:Cyclin B1 / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D059566:M Phase Cell Cycle Checkpoints; D008540:Meiosis; D049469:Meiotic Prophase I; D008677:Metaphase; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D056744:Cyclin B1; C577585:Fzr1 protein, mouse; D034741:RNA, Small Interfering; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse