title: Phosphorylation of threonine 3 on histone H3 by haspin kinase is required for meiosis I in mouse oocytes.
abstract: Meiosis I (MI), the division that generates haploids, is prone to errors that lead to aneuploidy in females. Haspin is a kinase that phosphorylates histone H3 on threonine 3, thereby recruiting Aurora kinase B (AURKB) and the chromosomal passenger complex (CPC) to kinetochores to regulate mitosis. Haspin and AURKC, an AURKB homolog, are enriched in germ cells, yet their significance in regulating MI is not fully understood. Using inhibitors and overexpression approaches, we show a role for haspin during MI in mouse oocytes. Haspin-perturbed oocytes display abnormalities in chromosome morphology and alignment, improper kinetochore-microtubule attachments at metaphase I and aneuploidy at metaphase II. Unlike in mitosis, kinetochore localization remained intact, whereas the distribution of the CPC along chromosomes was absent. The meiotic defects following haspin inhibition were similar to those observed in oocytes where AURKC was inhibited, suggesting that the correction of microtubule attachments during MI requires AURKC along chromosome arms rather than at kinetochores. Our data implicate haspin as a regulator of the CPC and chromosome segregation during MI, while highlighting important differences in how chromosome segregation is regulated between MI and mitosis.
authors.affiliation: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Nguyen
authors.affiliation: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Gentilello
authors.affiliation: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Ahmed Z
authors.initials: AZ
authors.lastname: Balboula
authors.affiliation: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Vibha
authors.initials: V
authors.lastname: Shrivastava
authors.affiliation: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Ohring
authors.affiliation: Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA schindler@biology.rutgers.edu.
authors.forename: Karen
authors.initials: K
authors.lastname: Schindler
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000782:Aneuploidy; D000818:Animals; D064108:Aurora Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D020090:Chromosome Segregation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006657:Histones / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000201:enzymology; D049469:Meiotic Prophase I / Q000187:drug effects; D051379:Mice; D008870:Microtubules / Q000201:enzymology; D046912:Multiprotein Complexes / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction; D013912:Threonine; D013997:Time Factors; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C530657:Haspin protein, mouse; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors; C108312:condensin complexes; D013912:Threonine; C576928:Aurkc protein, mouse; D064108:Aurora Kinase C; D017346:Protein Serine-Threonine Kinases; D000251:Adenosine Triphosphatases
keywords: Aurora kinase; Haspin kinase; Histone phosphorylation; Meiosis I; Meiotic maturation; Oocyte