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How oocytes try to get it right: spindle checkpoint control in meiosis

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Abstract

The generation of a viable, diploid organism depends on the formation of haploid gametes, oocytes, and spermatocytes, with the correct number of chromosomes. Halving the genome requires the execution of two consecutive specialized cell divisions named meiosis I and II. Unfortunately, and in contrast to male meiosis, chromosome segregation in oocytes is error prone, with human oocytes being extraordinarily “meiotically challenged”. Aneuploid oocytes, that are with the wrong number of chromosomes, give rise to aneuploid embryos when fertilized. In humans, most aneuploidies are lethal and result in spontaneous abortions. However, some trisomies survive to birth or even adulthood, such as the well-known trisomy 21, which gives rise to Down syndrome (Nagaoka et al. in Nat Rev Genet 13:493–504, 2012). A staggering 20–25 % of oocytes ready to be fertilized are aneuploid in humans. If this were not bad enough, there is an additional increase in meiotic missegregations as women get closer to menopause. A woman above 40 has a risk of more than 30 % of getting pregnant with a trisomic child. Worse still, in industrialized western societies, child birth is delayed, with women getting their first child later in life than ever. This trend has led to an increase of trisomic pregnancies by 70 % in the last 30 years (Nagaoka et al. in Nat Rev Genet 13:493–504, 2012; Schmidt et al. in Hum Reprod Update 18:29–43, 2012). To understand why errors occur so frequently during the meiotic divisions in oocytes, we review here the molecular mechanisms at works to control chromosome segregation during meiosis. An important mitotic control mechanism, namely the spindle assembly checkpoint or SAC, has been adapted to the special requirements of the meiotic divisions, and this review will focus on our current knowledge of SAC control in mammalian oocytes. Knowledge on how chromosome segregation is controlled in mammalian oocytes may help to identify risk factors important for questions related to human reproductive health.

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References

  • Almonacid M, Terret ME, Verlhac MH (2014) Actin-based spindle positioning: new insights from female gametes. J Cell Sci 127:477–483

    Article  CAS  PubMed  Google Scholar 

  • Aravamudhan P, Goldfarb AA, Joglekar AP (2015) The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signalling. Nat Cell Biol 17:868–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baker DJ, Jeganathan KB, Cameron JD, Thompson M, Juneja S, Kopecka A, Kumar R, Jenkins RB, de Groen PC, Roche P, van Deursen JM (2004) BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nat Genet 36:744–749

    Article  CAS  PubMed  Google Scholar 

  • Balboula AZ, Schindler K (2014) Selective disruption of aurora C kinase reveals distinct functions from aurora B kinase during meiosis in mouse oocytes. PLoS Genet 10, e1004194

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Batiha O, Swan A (2012) Evidence that the spindle assembly checkpoint does not regulate APC(Fzy) activity in Drosophila female meiosis. Genome / National Research Council Canada = Genome / Conseil national de recherches Canada 55:63–67

    Article  CAS  PubMed  Google Scholar 

  • Buffin E, Emre D, Karess RE (2007) Flies without a spindle checkpoint. Nat Cell Biol 9:565–572

    Article  CAS  PubMed  Google Scholar 

  • Chaigne A, Campillo C, Gov NS, Voituriez R, Sykes C, Verlhac MH, Terret ME (2015) A narrow window of cortical tension guides asymmetric spindle positioning in the mouse oocyte. Nat Commun 6:6027

    Article  CAS  PubMed  Google Scholar 

  • Chambon JP, Hached K, Wassmann K (2013) Chromosome spreads with centromere staining in mouse oocytes. Methods Mol Biol 957:203–212

    Article  CAS  PubMed  Google Scholar 

  • Chen RH, Waters JC, Salmon ED, Murray AW (1996) Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores. Science 274:242–246

    Article  CAS  PubMed  Google Scholar 

  • Chiang T, Duncan FE, Schindler K, Schultz RM, Lampson MA (2010) Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes. Curr Biol 20:1522–1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collin P, Nashchekina O, Walker R, Pines J (2013) The spindle assembly checkpoint works like a rheostat rather than a toggle switch. Nat Cell Biol 15:1378–1385

    Article  CAS  PubMed  Google Scholar 

  • Daniel K, Lange J, Hached K, Fu J, Anastassiadis K, Roig I, Cooke HJ, Stewart AF, Wassmann K, Jasin M, Keeney S, Toth A (2011) Meiotic homologue alignment and its quality surveillance are controlled by mouse HORMAD1. Nat Cell Biol 13:599–610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Danylevska A, Kovacovicova K, Awadova T, Anger M (2014) The frequency of precocious segregation of sister chromatids in mouse female meiosis I is affected by genetic background. Chromosome Res 22:365–373

    Article  CAS  PubMed  Google Scholar 

  • Darribère T (2003) Le développement d’un mammifère : la souris. Belin 19–71

  • Davie E (2012) A first child at 28 years old. Insee 1419

  • Davydenko O, Schultz RM, Lampson MA (2013) Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I. J Cell Biol 202:221–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dick AE, Gerlich DW (2013) Kinetic framework of spindle assembly checkpoint signalling. Nat Cell Biol 15:1370–1377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duncan FE, Chiang T, Schultz RM, Lampson MA (2009) Evidence that a defective spindle assembly checkpoint is not the primary cause of maternal age-associated aneuploidy in mouse eggs. Biol Reprod 81:768–776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Felix MA, Labbe JC, Doree M, Hunt T, Karsenti E (1990) Triggering of cyclin degradation in interphase extracts of amphibian eggs by cdc2 kinase. Nature 346:379–382

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Miranda G, Trakala M, Martin J, Escobar B, Gonzalez A, Ghyselinck NB, Ortega S, Canamero M, Perez de Castro I, Malumbres M (2011) Genetic disruption of aurora B uncovers an essential role for aurora C during early mammalian development. Development 138:2661–2672

    Article  CAS  PubMed  Google Scholar 

  • Foijer F, Xie SZ, Simon JE, Bakker PL, Conte N, Davis SH, Kregel E, Jonkers J, Bradley A, Sorger PK (2014) Chromosome instability induced by Mps1 and p53 mutation generates aggressive lymphomas exhibiting aneuploidy-induced stress. Proc Natl Acad Sci U S A 111:13427–13432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foley EA, Kapoor TM (2013) Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore. Nat Rev Mol Cell Biol 14:25–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gemzell CA (1962) Induction of ovulation with human pituitary gonadotrophins. Fertil Steril 13:153–168

    CAS  PubMed  Google Scholar 

  • Gomez R, Valdeolmillos A, Parra MT, Viera A, Carreiro C, Roncal F, Rufas JS, Barbero JL, Suja JA (2007) Mammalian SGO2 appears at the inner centromere domain and redistributes depending on tension across centromeres during meiosis II and mitosis. EMBO Rep 8:173–180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gorr IH, Reis A, Boos D, Wuhr M, Madgwick S, Jones KT, Stemmann O (2006) Essential CDK1-inhibitory role for separase during meiosis I in vertebrate oocytes. Nat Cell Biol 8:1035–1037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gui L, Homer H (2012) Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes. Development 139:1941–1946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hached K, Xie SZ, Buffin E, Cladiere D, Rachez C, Sacras M, Sorger PK, Wassmann K (2011) Mps1 at kinetochores is essential for female mouse meiosis I. Development 138:2261–2271

    Article  CAS  PubMed  Google Scholar 

  • Handyside AH (2012) Molecular origin of female meiotic aneuploidies. Biochim Biophys Acta 1822:1913–1920

    Article  CAS  PubMed  Google Scholar 

  • Hassold T, Hunt P (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2:280–291

    Article  CAS  PubMed  Google Scholar 

  • Hassold T, Abruzzo M, Adkins K, Griffin D, Merrill M, Millie E, Saker D, Shen J, Zaragoza M (1996) Human aneuploidy: incidence, origin, and etiology. Environ Mol Mutagen 28:167–175

    Article  CAS  PubMed  Google Scholar 

  • Hauf S (2013) The spindle assembly checkpoint: progress and persistent puzzles. Biochem Soc Trans 41:1755–1760

    Article  CAS  PubMed  Google Scholar 

  • Hiruma Y, Sacristan C, Pachis ST, Adamopoulos A, Kuijt T, Ubbink M, von Castelmur E, Perrakis A, Kops GJ (2015) CELL DIVISION CYCLE. Competition between MPS1 and microtubules at kinetochores regulates spindle checkpoint signaling. Science 348:1264–1267

    Article  CAS  PubMed  Google Scholar 

  • Homer HA, McDougall A, Levasseur M, Murdoch AP, Herbert M (2005a) Mad2 is required for inhibiting securin and cyclin B degradation following spindle depolymerisation in meiosis I mouse oocytes. Reproduction 130:829–843

    Article  CAS  PubMed  Google Scholar 

  • Homer HA, McDougall A, Levasseur M, Yallop K, Murdoch AP, Herbert M (2005b) Mad2 prevents aneuploidy and premature proteolysis of cyclin B and securin during meiosis I in mouse oocytes. Genes Dev 19:202–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Homer H, Gui L, Carroll J (2009) A spindle assembly checkpoint protein functions in prophase I arrest and prometaphase progression. Science 326:991–994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishiguro T, Tanaka K, Sakuno T, Watanabe Y (2010) Shugoshin-PP2A counteracts casein-kinase-1-dependent cleavage of Rec8 by separase. Nat Cell Biol 12:500–506

    Article  CAS  PubMed  Google Scholar 

  • Jeganathan KB, van Deursen JM (2006) Differential mitotic checkpoint protein requirements in somatic and germ cells. Biochem Soc Trans 34:583–586

    Article  CAS  PubMed  Google Scholar 

  • Ji Z, Gao H, Yu H (2015) CELL DIVISION CYCLE. Kinetochore attachment sensed by competitive Mps1 and microtubule binding to Ndc80C. Science 348:1260–1264

    Article  CAS  PubMed  Google Scholar 

  • Jones KT, Lane SI (2013) Molecular causes of aneuploidy in mammalian eggs. Development 140:3719–3730

    Article  CAS  PubMed  Google Scholar 

  • Kabeche L, Compton DA (2013) Cyclin A regulates kinetochore microtubules to promote faithful chromosome segregation. Nature 502:110–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katis VL, Lipp JJ, Imre R, Bogdanova A, Okaz E, Habermann B, Mechtler K, Nasmyth K, Zachariae W (2010) Rec8 phosphorylation by casein kinase 1 and Cdc7-Dbf4 kinase regulates cohesin cleavage by separase during meiosis. Dev Cell 18:397–409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawashima SA, Yamagishi Y, Honda T, Ishiguro K, Watanabe Y (2010) Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin. Science 327:172–177

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Ishiguro K, Nambu A, Akiyoshi B, Yokobayashi S, Kagami A, Ishiguro T, Pendas AM, Takeda N, Sakakibara Y, Kitajima TS, Tanno Y, Sakuno T, Watanabe Y (2015) Meikin is a conserved regulator of meiosis-I-specific kinetochore function. Nature 517:466–471

    Article  CAS  PubMed  Google Scholar 

  • Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y (2006) Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 441:46–52

    Article  CAS  PubMed  Google Scholar 

  • Kitajima TS, Ohsugi M, Ellenberg J (2011) Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes. Cell 146:568–581

    Article  CAS  PubMed  Google Scholar 

  • Kolano A, Brunet S, Silk AD, Cleveland DW, Verlhac MH (2012) Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension. Proc Natl Acad Sci U S A 109:E1858–E1867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kouznetsova A, Lister L, Nordenskjold M, Herbert M, Hoog C (2007) Bi-orientation of achiasmatic chromosomes in meiosis I oocytes contributes to aneuploidy in mice. Nat Genet 39:966–968

    Article  CAS  PubMed  Google Scholar 

  • Kouznetsova A, Hernandez-Hernandez A, Hoog C (2014) Merotelic attachments allow alignment and stabilization of chromatids in meiosis II oocytes. Nat Commun 5:4409

    Article  CAS  PubMed  Google Scholar 

  • Kruse T, Zhang G, Larsen MS, Lischetti T, Streicher W, Kragh Nielsen T, Bjorn SP, Nilsson J (2013) Direct binding between BubR1 and B56-PP2A phosphatase complexes regulate mitotic progression. J Cell Sci 126:1086–1092

    Article  CAS  PubMed  Google Scholar 

  • Lane SI, Jones KT (2014) Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse oocytes. Nat Commun 5:3444

    Article  PubMed  CAS  Google Scholar 

  • Lane SI, Chang HY, Jennings PC, Jones KT (2010) The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint. Reproduction 140:521–530

    Article  CAS  PubMed  Google Scholar 

  • Lane SI, Yun Y, Jones KT (2012) Timing of anaphase-promoting complex activation in mouse oocytes is predicted by microtubule-kinetochore attachment but not by bivalent alignment or tension. Development 139:1947–1955

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Kitajima TS, Tanno Y, Yoshida K, Morita T, Miyano T, Miyake M, Watanabe Y (2008) Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells. Nat Cell Biol 10:42–52

    Article  CAS  PubMed  Google Scholar 

  • Leland S, Nagarajan P, Polyzos A, Thomas S, Samaan G, Donnell R, Marchetti F, Venkatachalam S (2009) Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice. Proc Natl Acad Sci U S A 106:12776–12781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • LeMaire-Adkins R, Radke K, Hunt PA (1997) Lack of checkpoint control at the metaphase/anaphase transition: a mechanism of meiotic nondisjunction in mammalian females. J Cell Biol 139:1611–1619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li R, Albertini DF (2013) The road to maturation: somatic cell interaction and self-organization of the mammalian oocyte. Nature Rev 14:141–152

    Article  CAS  Google Scholar 

  • Li M, Li S, Yuan J, Wang ZB, Sun SC, Schatten H, Sun QY (2009) Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis. PLoS One 4, e7701

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lister LM, Kouznetsova A, Hyslop LA, Kalleas D, Pace SL, Barel JC, Nathan A, Floros V, Adelfalk C, Watanabe Y, Jessberger R, Kirkwood TB, Hoog C, Herbert M (2010) Age-related meiotic segregation errors in Mammalian oocytes are preceded by depletion of cohesin and Sgo2. Curr Biol 20:1511–1521

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Keefe DL (2002) Ageing-associated aberration in meiosis of oocytes from senescence-accelerated mice. Hum Reprod 17:2678–2685

    Article  CAS  PubMed  Google Scholar 

  • Liu D, Vader G, Vromans MJ, Lampson MA, Lens SM (2009) Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates. Science 323:1350–1353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu D, Shao H, Wang H, Liu XJ (2014) Meiosis I in Xenopus oocytes is not error-prone despite lacking spindle assembly checkpoint. Cell Cycle 13:1602–1606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Llano E, Gomez R, Gutierrez-Caballero C, Herran Y, Sanchez-Martin M, Vazquez-Quinones L, Hernandez T, de Alava E, Cuadrado A, Barbero JL, Suja JA, Pendas AM (2008) Shugoshin-2 is essential for the completion of meiosis but not for mitotic cell division in mice. Genes Dev 22:2400–2413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • London N, Biggins S (2014) Signalling dynamics in the spindle checkpoint response. Nat Rev Mol Cell Biol 15:736–747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo X, Tang Z, Rizo J, Yu H (2002) The mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either mad1 or cdc20. Mol Cell 9:59–71

    Article  PubMed  Google Scholar 

  • Maciejowski J, George KA, Terret ME, Zhang C, Shokat KM, Jallepalli PV (2010) Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling. J Cell Biol 190:89–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Madgwick S, Hansen DV, Levasseur M, Jackson PK, Jones KT (2006) Mouse Emi2 is required to enter meiosis II by reestablishing cyclin B1 during interkinesis. J Cell Biol 174:791–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maiato H, DeLuca J, Salmon ED, Earnshaw WC (2004) The dynamic kinetochore-microtubule interface. J Cell Sci 117:5461–5477

    Article  CAS  PubMed  Google Scholar 

  • McGuinness BE, Anger M, Kouznetsova A, Gil-Bernabe AM, Helmhart W, Kudo NR, Wuensche A, Taylor S, Hoog C, Novak B, Nasmyth K (2009) Regulation of APC/C activity in oocytes by a Bub1-dependent spindle assembly checkpoint. Curr Biol 19:369–380

    Article  CAS  PubMed  Google Scholar 

  • Meraldi P, Draviam VM, Sorger PK (2004) Timing and checkpoints in the regulation of mitotic progression. Dev Cell 7:45–60

    Article  CAS  PubMed  Google Scholar 

  • Merriman JA, Lane SI, Holt JE, Jennings PC, Garcia-Higuera I, Moreno S, McLaughlin EA, Jones KT (2013) Reduced chromosome cohesion measured by interkinetochore distance is associated with aneuploidy even in oocytes from young mice. Biol Reprod 88:31

    Article  PubMed  CAS  Google Scholar 

  • Michel LS, Liberal V, Chatterjee A, Kirchwegger R, Pasche B, Gerald W, Dobles M, Sorger PK, Murty VVVS, Benezra R (2001) MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature 409:355–359

    Article  CAS  PubMed  Google Scholar 

  • Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8:379–393

    Article  CAS  PubMed  Google Scholar 

  • Nagaoka SI, Hodges CA, Albertini DF, Hunt PA (2011) Oocyte-specific differences in cell-cycle control create an innate susceptibility to meiotic errors. Curr Biol 21:651–657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagaoka SI, Hassold TJ, Hunt PA (2012) Human aneuploidy: mechanisms and new insights into an age-old problem. Nat Rev Genet 13:493–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen AL, Gentilello AS, Balboula AZ, Shrivastava V, Ohring J, Schindler K (2014) Phosphorylation of threonine 3 on histone H3 by haspin kinase is required for meiosis I in mouse oocytes. J Cell Sci 127:5066–5078

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Niault T, Hached K, Sotillo R, Sorger PK, Maro B, Benezra R, Wassmann K (2007) Changing Mad2 levels affects chromosome segregation and spindle assembly checkpoint control in female mouse meiosis I. PLoS One 2, e1165

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nijenhuis W, Vallardi G, Teixeira A, Kops GJ, Saurin AT (2014) Negative feedback at kinetochores underlies a responsive spindle checkpoint signal. Nat Cell Biol 16:1257–1264

    Article  CAS  PubMed  Google Scholar 

  • O’Connell CB, Loncarek J, Hergert P, Kourtidis A, Conklin DS, Khodjakov A (2008) The spindle assembly checkpoint is satisfied in the absence of interkinetochore tension during mitosis with unreplicated genomes. J Cell Biol 183:29–36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Peters JM, Tedeschi A, Schmitz J (2008) The cohesin complex and its roles in chromosome biology. Genes Dev 22:3089–3114

    Article  CAS  PubMed  Google Scholar 

  • Petronczki M, Siomos MF, Nasmyth K (2003) Un menage a quatre: the molecular biology of chromosome segregation in meiosis. Cell 112:423–440

    Article  CAS  PubMed  Google Scholar 

  • Pinsky BA, Biggins S (2005) The spindle checkpoint: tension versus attachment. Trends Cell Biol 15:486–493

    Article  CAS  PubMed  Google Scholar 

  • Rattani A, Wolna M, Ploquin M, Helmhart W, Morrone S, Mayer B, Godwin J, Xu W, Stemmann O, Pendas A, Nasmyth K (2013) Sgol2 provides a regulatory platform that coordinates essential cell cycle processes during meiosis I in oocytes. eLife 2, e01133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rattani A, Vinod PK, Godwin J, Tachibana-Konwalski K, Wolna M, Malumbres M, Novak B, Nasmyth K (2014) Dependency of the spindle assembly checkpoint on Cdk1 renders the anaphase transition irreversible. Curr Biol 24:630–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ricke RM, Jeganathan KB, Malureanu L, Harrison AM, van Deursen JM (2012) Bub1 kinase activity drives error correction and mitotic checkpoint control but not tumor suppression. J Cell Biol 199:931–949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riedel CG, Katis VL, Katou Y, Mori S, Itoh T, Helmhart W, Galova M, Petronczki M, Gregan J, Cetin B, Mudrak I, Ogris E, Mechtler K, Pelletier L, Buchholz F, Shirahige K, Nasmyth K (2006) Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature 441:53–61

    Article  CAS  PubMed  Google Scholar 

  • Rieder CL, Cole RW, Khodjakov A, Sluder G (1995) The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores. J Cell Biol 130:941–948

    Article  CAS  PubMed  Google Scholar 

  • Riris S, Webster P, Homer H (2014) Digital multiplexed mRNA analysis of functionally important genes in single human oocytes and correlation of changes in transcript levels with oocyte protein expression. Fertil Steril 101:857–864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodriguez-Bravo V, Maciejowski J, Corona J, Buch HK, Collin P, Kanemaki MT, Shah JV, Jallepalli PV (2014) Nuclear pores protect genome integrity by assembling a premitotic and Mad1-dependent anaphase inhibitor. Cell 156:1017–1031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rogers E, Bishop JD, Waddle JA, Schumacher JM, Lin R (2002) The aurora kinase AIR-2 functions in the release of chromosome cohesion in Caenorhabditis elegans meiosis. J Cell Biol 157:219–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rumpf C, Cipak L, Dudas A, Benko Z, Pozgajova M, Riedel CG, Ammerer G, Mechtler K, Gregan J (2010) Casein kinase 1 is required for efficient removal of Rec8 during meiosis I. Cell Cycle 9:2657–2662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sacristan C, Kops GJ (2015) Joined at the hip: kinetochores, microtubules, and spindle assembly checkpoint signaling. Trends Cell Biol 25:21–28

    Article  CAS  PubMed  Google Scholar 

  • Santaguida S, Tighe A, D’Alise AM, Taylor SS, Musacchio A (2010) Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine. J Cell Biol 190:73–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasai K, Katayama H, Stenoien DL, Fujii S, Honda R, Kimura M, Okano Y, Tatsuka M, Suzuki F, Nigg EA, Earnshaw WC, Brinkley WR, Sen S (2004) Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Cell Motil Cytoskeleton 59:249–263

    Article  CAS  PubMed  Google Scholar 

  • Sebestova J, Danylevska A, Novakova L, Kubelka M, Anger M (2012) Lack of response to unaligned chromosomes in mammalian female gametes. Cell Cycle 11:3011–3018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Severson AF, Meyer BJ (2014) Divergent kleisin subunits of cohesin specify mechanisms to tether and release meiotic chromosomes. eLife 3, e03467

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Severson AF, Ling L, van Zuylen V, Meyer BJ (2009) The axial element protein HTP-3 promotes cohesin loading and meiotic axis assembly in C. elegans to implement the meiotic program of chromosome segregation. Genes Dev 23:1763–1778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao H, Li R, Ma C, Chen E, Liu XJ (2013) Xenopus oocyte meiosis lacks spindle assembly checkpoint control. J Cell Biol 201:191–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siomos MF, Badrinath A, Pasierbek P, Livingstone D, White J, Glotzer M, Nasmyth K (2001) Separase is required for chromosome segregation during meiosis I in Caenorhabditis elegans. Curr Biol 11:1825–1835

    Article  CAS  PubMed  Google Scholar 

  • Slattery SD, Moore RV, Brinkley BR, Hall RM (2008) Aurora-C and Aurora-B share phosphorylation and regulation of CENP-A and Borealin during mitosis. Cell Cycle 7:787–795

    Article  CAS  PubMed  Google Scholar 

  • Slattery SD, Mancini MA, Brinkley BR, Hall RM (2009) Aurora-C kinase supports mitotic progression in the absence of Aurora-B. Cell Cycle 8:2984–2994

    Article  PubMed  Google Scholar 

  • Stukenberg PT, Burke DJ (2015) Connecting the microtubule attachment status of each kinetochore to cell cycle arrest through the spindle assembly checkpoint. Chromosoma

  • Suijkerbuijk SJ, Vleugel M, Teixeira A, Kops GJ (2012) Integration of kinase and phosphatase activities by BUBR1 ensures formation of stable kinetochore-microtubule attachments. Dev Cell 23:745–755

    Article  CAS  PubMed  Google Scholar 

  • Sullivan M, Morgan DO (2007) Finishing mitosis, one step at a time. Nat Rev Mol Cell Biol 8:894–903

    Article  CAS  PubMed  Google Scholar 

  • Sun SC, Kim NH (2012) Spindle assembly checkpoint and its regulators in meiosis. Hum Reprod Update 18:60–72

    Article  CAS  PubMed  Google Scholar 

  • Tachibana-Konwalski K, Godwin J, van der Weyden L, Champion L, Kudo NR, Adams DJ, Nasmyth K (2010) Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes. Genes Dev 24:2505–2516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tachibana-Konwalski K, Godwin J, Borsos M, Rattani A, Adams DJ, Nasmyth K (2013) Spindle assembly checkpoint of oocytes depends on a kinetochore structure determined by cohesin in meiosis I. Curr Biol 23:2534–2539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang Z, Bharadwaj R, Li B, Yu H (2001) Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. Dev Cell 1:227–237

    Article  CAS  PubMed  Google Scholar 

  • Tang CJ, Lin CY, Tang TK (2006) Dynamic localization and functional implications of Aurora-C kinase during male mouse meiosis. Dev Biol 290:398–410

    Article  CAS  PubMed  Google Scholar 

  • Terret ME, Wassmann K (2008) Meiotic weakness : the first division. Med Sci (Paris) 24:197–204

    Article  Google Scholar 

  • Touati SA, Cladiere D, Lister LM, Leontiou I, Chambon JP, Rattani A, Bottger F, Stemmann O, Nasmyth K, Herbert M, Wassmann K (2012) Cyclin A2 Is required for sister chromatid segregation, but not separase control, in mouse oocyte meiosis. Cell Rep

  • Touati SA, Buffin E, Cladiere D, Hached K, Rachez C, van Deursen JM, Wassmann K (2015) Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest. Nat Commun 6:6946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsurumi C, Hoffmann S, Geley S, Graeser R, Polanski Z (2004) The spindle assembly checkpoint is not essential for CSF arrest of mouse oocytes. J Cell Biol 167:1037–1050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tunquist BJ, Schwab MS, Chen LG, Maller JL (2002) The spindle checkpoint kinase bub1 and cyclin e/cdk2 both contribute to the establishment of meiotic metaphase arrest by cytostatic factor. Curr Biol 12:1027–1033

    Article  CAS  PubMed  Google Scholar 

  • Tunquist BJ, Eyers PA, Chen LG, Lewellyn AL, Maller JL (2003) Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest. J Cell Biol 163:1231–1242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uhlmann F (2003) Chromosome cohesion and separation: from men and molecules. Curr Biol 13:R104–R114

    Article  CAS  PubMed  Google Scholar 

  • van der Waal MS, Hengeveld RC, van der Horst A, Lens SM (2012) Cell division control by the chromosomal passenger complex. Exp Cell Res 318:1407–1420

    Article  PubMed  CAS  Google Scholar 

  • Vera M, Peinado V, Al-Asmar N, Gruhn J, Rodrigo L, Hassold T, Rubio C (2012) Human male meiosis and sperm aneuploidies. InTech, Bookchapter in The causes and consequences of aneuploidy in eukaryotic cells (Editor: Z. Storchova)

  • Vleugel M, Hoogendoorn E, Snel B, Kops GJ (2012) Evolution and function of the mitotic checkpoint. Dev Cell 23:239–250

    Article  CAS  PubMed  Google Scholar 

  • Wang JY, Lei ZL, Nan CL, Yin S, Liu J, Hou Y, Li YL, Chen DY, Sun QY (2007) RNA Interference as a tool to study the function of MAD2 in mouse oocyte meiotic maturation. Mol Reprod Dev 74:116–124

    Article  CAS  PubMed  Google Scholar 

  • Wassmann K (2013) Sister chromatid segregation in meiosis II: deprotection through phosphorylation. Cell Cycle 12:1352–1359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wassmann K, Benezra R (1998) Mad2 transiently associates with an APC/p55Cdc complex during mitosis. Proc Natl Acad Sci U S A 95:11193–11198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wassmann K, Liberal V, Benezra R (2003a) Mad2 phosphorylation regulates its association with Mad1 and the APC/C. EMBO J 22:797–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wassmann K, Niault T, Maro B (2003b) Metaphase I arrest upon activation of the Mad2-dependent spindle checkpoint in mouse oocytes. Curr Biol 13:1596–1608

    Article  CAS  PubMed  Google Scholar 

  • Watanabe Y (2012) Geometry and force behind kinetochore orientation: lessons from meiosis. Nat Rev Mol Cell Biol 13:370–382

    Article  CAS  PubMed  Google Scholar 

  • Wei L, Liang XW, Zhang QH, Li M, Yuan J, Li S, Sun SC, Ouyang YC, Schatten H, Sun QY (2009) BubR1 is a spindle assembly checkpoint protein regulating meiotic cell cycle progression of mouse oocyte. Cell cycle Georgetown: 1112–1121

  • Woods LM, Hodges CA, Baart E, Baker SM, Liskay M, Hunt PA (1999) Chromosomal influence on meiotic spindle assembly: abnormal meiosis I in female Mlh1 mutant mice. J Cell Biol 145:1395–1406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu JQ, Kornbluth S (2008) Across the meiotic divide—CSF activity in the post-Emi2/XErp1 era. J Cell Sci 121:3509–3514

    Article  CAS  PubMed  Google Scholar 

  • Yang Q, Ferrell JE Jr (2013) The Cdk1-APC/C cell cycle oscillator circuit functions as a time-delayed, ultrasensitive switch. Nat Cell Biol 15:519–525

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang KT, Li SK, Chang CC, Tang CJ, Lin YN, Lee SC, Tang TK (2010) Aurora-C kinase deficiency causes cytokinesis failure in meiosis I and production of large polyploid oocytes in mice. Mol Biol Cell 21:2371–2383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin S, Wang Q, Liu JH, Ai JS, Liang CG, Hou Y, Chen DY, Schatten H, Sun QY (2006) Bub1 prevents chromosome misalignment and precocious anaphase during mouse oocyte meiosis. Cell Cycle 5:2130–2137

    Article  CAS  PubMed  Google Scholar 

  • Yun Y, Lane SI, Jones KT (2014) Premature dyad separation in meiosis II is the major segregation error with maternal age in mouse oocytes. Development 141:199–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang D, Li M, Ma W, Hou Y, Li YH, Li SW, Sun QY, Wang WH (2005) Localization of mitotic arrest deficient 1 (MAD1) in mouse oocytes during the first meiosis and its functions as a spindle checkpoint protein. Biol Reprod 72:58–68

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Work in the lab of K. Wassmann is supported by a grant from the Agence Nationale de la Recherche (ANR-12-BSV2-0005-01), the Centre National de la Recherche Scientifique (CNRS), and Université Paris 6. We thank E. Buffin, A. Vallot, and W. El Yakoubi for discussion and comments on the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest. For this review article, no studies with human participants or animals were performed by any of the authors.

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Correspondence to Katja Wassmann.

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This article is part of a Special Issue on “Recent advances in meiotic chromosome structure, recombination and segregation” edited by Marco Barchi, Paula Cohen and Scott Keeney.

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Touati, S.A., Wassmann, K. How oocytes try to get it right: spindle checkpoint control in meiosis. Chromosoma 125, 321–335 (2016). https://doi.org/10.1007/s00412-015-0536-7

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  • DOI: https://doi.org/10.1007/s00412-015-0536-7

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