title: Phosphorylation of histone H3 serine 10 in early mouse embryos: active phosphorylation at late S phase and differential effects of ZM447439 on first two embryonic mitoses.
abstract: Cell division in mammalian cells is regulated by Aurora kinases. The activity of Aurora A is indispensable for correct function of centrosomes and proper spindle formation, while Aurora B for chromosome biorientation and separation. Aurora B is also responsible for the phosphorylation of histone H3 serine 10 (H3S10Ph) from G2 to metaphase. Data concerning the Aurora B activity and H3S10Ph in embryonic cells are limited to primordial and maturing oocytes and advanced pronuclei in zygotes. In the present study we have analyzed H3S10Ph in 1- and 2-cell mouse embryos. We show that H3S10 remains phosphorylated at anaphase and telophase of the second meiotic division, as well as during the anaphase and telophase of the first and second embryonic mitoses. At late G1 H3S10 is dephosphorylated and subsequently phosphorylated de novo at late S phase of the first and second cell cycle. These results show that the H3S10 phosphorylation/dephosphorylation cycle in embryonic cells is different than in somatic cells. The behaviour of thymocyte G0 nuclei introduced into ovulated oocytes and early 1-cell parthenogenotes confirms that kinases responsible for de novo H3S10 phosphorylation, most probably Aurora B,  are active until G1 of the first cell cycle of mouse embryo. The inhibition of Aurora kinases by ZM447439 caused abnormalities both in the first and second mitoses. However, the disturbances in each division differed, suggesting important differences in the control of these mitoses. In ZM447439-treated mitotic zygotes Mad2 protein remained continuously present on kinetochores, what confirmed that spindle checkpoint remained active.
authors.affiliation: Department of Embryology, Institute of Zoology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Teperek-Tkacz
authors.forename: Maciej
authors.initials: M
authors.lastname: Meglicki
authors.forename: Michal
authors.initials: M
authors.lastname: Pasternak
authors.forename: Jacek Z
authors.initials: JZ
authors.lastname: Kubiak
authors.forename: Ewa
authors.initials: E
authors.lastname: Borsuk
mesh_terms: D000705:Anaphase; D000818:Animals; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000201:enzymology*; D005260:Female; D016193:G1 Phase; D006657:Histones / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism; D064246:Mad2 Proteins; D008297:Male; D051379:Mice; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D016196:S Phase; D012694:Serine / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D013692:Telophase
chemical_list: C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; D001549:Benzamides; D018797:Cell Cycle Proteins; D006657:Histones; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; D011799:Quinazolines; D012694:Serine; C576918:Aurka protein, mouse; C576924:Aurkb protein, mouse; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases