title: Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis.
abstract: In mitosis, the spindle assembly checkpoint (SAC) prevents anaphase onset until all chromosomes have been attached to the spindle microtubules and aligned correctly at the equatorial metaphase plate. The major checkpoint proteins in mitosis consist of mitotic arrest-deficient (Mad)1-3, budding uninhibited by benzimidazole (Bub)1, Bub3, and monopolar spindle 1(Mps1). During meiosis, for the formation of a haploid gamete, two consecutive rounds of chromosome segregation occur with only one round of DNA replication. To pull homologous chromosomes to opposite spindle poles during meiosis I, both sister kinetochores of a homologue must face toward the same pole which is very different from mitosis and meiosis II. As a core member of checkpoint proteins, the individual role of Bub3 in mammalian oocyte meiosis is unclear. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of Bub3 in mouse oocyte meiosis. Our data showed that overexpressed Bub3 inhibited meiotic metaphase-anaphase transition by preventing homologous chromosome and sister chromatid segregations in meiosis I and II, respectively. Misaligned chromosomes, abnormal polar body and double polar bodies were observed in Bub3 knock-down oocytes, causing aneuploidy. Furthermore, through cold treatment combined with Bub3 overexpression, we found that overexpressed Bub3 affected the attachments of microtubules and kinetochores during metaphase-anaphase transition. We propose that as a member of SAC, Bub3 is required for regulation of both meiosis I and II, and is potentially involved in kinetochore-microtubule attachment in mammalian oocytes.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.forename: Ju
authors.initials: J
authors.lastname: Yuan
authors.forename: Zhen-Bo
authors.initials: ZB
authors.lastname: Wang
authors.forename: Shao-Chen
authors.initials: SC
authors.lastname: Sun
authors.forename: Heide
authors.initials: H
authors.lastname: Schatten
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Sun
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone; D020090:Chromosome Segregation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D008813:Mice, Inbred ICR; D015739:Nocodazole / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology*; D011003:Ploidies; D000075223:Poly-ADP-Ribose Binding Proteins; D034622:RNA Interference; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: C489445:Bub3 protein, mouse; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000075223:Poly-ADP-Ribose Binding Proteins; D050257:Tubulin Modulators; D015739:Nocodazole