BubR1 is a spindle assembly checkpoint protein regulating meiotic cell cycle progression of mouse oocyte.
BubR1 (Bub1-related kinase or MAD3/Bub1b) is an essential component of the spindle assembly checkpoint (SAC) and plays an important role in kinetochore localization of other spindle checkpoint proteins in mitosis. But its roles in mammalian oocyte meiosis are unclear. In the present study, we examined the expression, localization and function of BubR1 during mouse oocyte meiotic maturation. The expression level of BubR1 increased progressively from germinal vesicle to metaphase II stages. Immunofluorescent analysis showed that BubR1 localized to kinetochores from the germinal vesicle breakdown to the prometaphase I stages, co-localizing with polo-like kinase 1, while it disappeared from the kinetochores at the metaphase I stage. Spindle disruption by nocodazole treatment caused relocation of BubR1 to kinetochores at metaphase I, anaphase I and metaphase II stages; spindle microtubules were disrupted by low temperature treatment in the BubR1-depleted oocytes in meiosis I, suggesting that BubR1 monitors kinetochore-microtubule (K-MT) attachments. Over-expression of exogenous BubR1 arrested oocyte meiosis maturation at the M I stage or earlier; in contrast, dominant-negative BubR1 and BubR1 depletion accelerated meiotic progression. In the BubR1-depleted oocytes, higher percentage of chromosome misalignment was observed and more oocytes overrode the M I stage arrest induced by low concentration of nocodazole. Our data suggest that BubR1 is a spindle assembly checkpoint protein regulating meiotic progression of oocytes.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Science, Beijing, China.
Liang
L
Wei
Xing-Wei
XW
Liang
Qing-Hua
QH
Zhang
Mo
M
Li
Ju
J
Yuan
Sen
S
Li
Shao-Chen
SC
Sun
Ying-Chun
YC
Ouyang
Heide
H
Schatten
Qing-Yuan
QY
Sun
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D023902:Chromosome Pairing / Q000187:drug effects; D005799:Genes, Dominant / Q000235:genetics; D018386:Kinetochores / Q000187:drug effects / Q000378:metabolism; D008540:Meiosis / Q000187:drug effects; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects / Q000201:enzymology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D015739:Nocodazole; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C584278:Bub1b protein, mouse; C584281:Bub1 protein, mouse; C090464:Bub1 spindle checkpoint protein