Aurora kinase B, epigenetic state of centromeric heterochromatin and chiasma resolution in oocytes.
Aurora kinases comprise a family of phosphoproteins performing multiple functions in mitosis and meiosis. Because Aurora kinase B (AURKB) expression is altered in aged oocytes and there is only limited information on its function in meiosis, it was decided to study the spatial distribution and co-localization of AURKB with other regulatory proteins at centromeres during mouse oocyte maturation. AURKB associates with chromosomes after germinal vesicle breakdown, is enriched at centromeres from prometaphase I and transits to the spindle midzone at late anaphase I. Preferential inhibition of AURKB by low concentrations of ZM 447439 inhibitor prevents polar body formation and affects spindle formation and chromosome congression at meiosis I, associated with expression of BubR1 checkpoint protein at kinetochores. Release of cohesion between sister chromatids appears inhibited resulting in failure of chiasma resolution in oocytes progressing to anaphase I. Concomitantly, the inhibitor reduces histone H3 lysine 9 trimethylation at centromeric heterochromatin and affects chromosome condensation. The cytokinesis arrest protects young, healthy oocytes from errors in chromosome segregation although increasing polyploidy. This study shows that changes in activity of AURKB may increase risks for chromosome non-disjunction and aneuploidy in mammalian oocytes, irrespective of age.
Vogt
E
E
University of Bielefeld, Gene Technology/Microbiology, Bielefeld, Germany.
Kipp
A
A
Eichenlaub-Ritter
U
U
D000782:Aneuploidy; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001549:Benzamides / Q000494:pharmacology; D002503:Centromere / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D020090:Chromosome Segregation / Q000187:drug effects / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D006570:Heterochromatin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000037:antagonists & inhibitors / Q000378:metabolism; D008540:Meiosis / Q000187:drug effects / Q000235:genetics; D051379:Mice; D009630:Nondisjunction, Genetic / Q000235:genetics; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D009866:Oogenesis / Q000187:drug effects / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism
C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; D001549:Benzamides; D006570:Heterochromatin; D006657:Histones; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases