Aurora kinase B modulates chromosome alignment in mouse oocytes.
The elevated incidence of aneuploidy in human oocytes warrants study of the molecular mechanisms regulating proper chromosome segregation. The Aurora kinases are a well-conserved family of serine/threonine kinases that are involved in proper chromosome segregation during mitosis and meiosis. Here we report the expression and localization of all three Aurora kinase homologs, AURKA, AURKB, and AURKC, during meiotic maturation of mouse oocytes. AURKA, the most abundantly expressed homolog, localizes to the spindle poles during meiosis I (MI) and meiosis II (MII), whereas AURKB is concentrated at kinetochores, specifically at metaphase of MI (Met I). The germ cell-specific homolog, AURKC, is found along the entire length of chromosomes during both meiotic divisions. Maturing oocytes in the presence of the small molecule pan-Aurora kinase inhibitor, ZM447439 results in defects in meiotic progression and chromosome alignment at both Met I and Met II. Over-expression of AURKB, but not AURKA or AURKC, rescues the chromosome alignment defect suggesting that AURKB is the primary Aurora kinase responsible for regulating chromosome dynamics during meiosis in mouse oocytes.
Shuda
Kristy
K
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Schindler
Karen
K
Ma
Jun
J
Schultz
Richard M
RM
Donovan
Peter J
PJ
D000704:Analysis of Variance; D000818:Animals; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D001549:Benzamides / Q000494:pharmacology; D020090:Chromosome Segregation / Q000187:drug effects / Q000502:physiology*; D002875:Chromosomes / Q000378:metabolism; D007150:Immunohistochemistry; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D022101:Microtubule-Organizing Center / Q000378:metabolism; D009865:Oocytes / Q000201:enzymology* / Q000648:ultrastructure*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology
C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; D001549:Benzamides; D011799:Quinazolines; C576917:AURKA protein, human; C576921:AURKB protein, human; C576927:AURKC protein, human; C576918:Aurka protein, mouse; C576924:Aurkb protein, mouse; C576928:Aurkc protein, mouse; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases