Phosphorylation of threonine 3 on histone H3 by Haspin kinase is required for meiosis I in mouse oocytes
| Autor: | Jacob Ohring, Karen Schindler, Ahmed Z. Balboula, Alexandra L. Nguyen, Amanda S. Gentilello, Vibha Shrivastava |
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| Rok vydání: | 2014 |
| Předmět: |
Threonine
Time Factors Protein Serine-Threonine Kinases Biology Transfection Microtubules Histones Chromosome segregation Mice Histone H3 Meiosis Chromosome Segregation Animals Aurora Kinase C Meiotic Prophase I Phosphorylation Kinetochores Protein Kinase Inhibitors Mitosis Cells Cultured Adenosine Triphosphatases Kinetochore Intracellular Signaling Peptides and Proteins Cell Biology Aneuploidy Molecular biology Cell biology DNA-Binding Proteins Protein Transport Histone phosphorylation Multiprotein Complexes Oocytes Female Aurora Kinase B Protein Processing Post-Translational Signal Transduction Research Article |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.158840 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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