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Spindle formation, chromosome segregation and the spindle checkpoint in mammalian oocytes and susceptibility to meiotic error

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Title: Spindle formation, chromosome segregation and the spindle checkpoint in mammalian oocytes and susceptibility to meiotic error
Authors: Vogt, E.1, Kirsch-Volders, M.2, Parry, J.3, Eichenlaub-Ritter, U.1 EiRi@uni-bielefeld.de
Source: Mutation Research - Genetic Toxicology & Environmental Mutagenesis. Mar2008, Vol. 651 Issue 1/2, p14-29. 16p.
Subject Terms: *Genetics, Spindle apparatus, Chromosomes, Genetic mutation
Abstract: Abstract: The spindle assembly checkpoint (SAC) monitors attachment to microtubules and tension on chromosomes in mitosis and meiosis. It represents a surveillance mechanism that halts cells in M-phase in the presence of unattached chromosomes, associated with accumulation of checkpoint components, in particular, Mad2, at the kinetochores. A complex between the anaphase promoting factor/cylosome (APC/C), its accessory protein Cdc20 and proteins of the SAC renders APC/C inactive, usually until all chromosomes are properly assembled at the spindle equator (chromosome congression) and under tension from spindle fibres. Upon release from the SAC the APC/C can target proteins like cyclin B and securin for degradation by the proteasome. Securin degradation causes activation of separase proteolytic enzyme, and in mitosis cleavage of cohesin proteins at the centromeres and arms of sister chromatids. In meiosis I only the cohesin proteins at the sister chromatid arms are cleaved. This requires meiosis specific components and tight regulation by kinase and phosphatase activities. There is no S-phase between meiotic divisions. Second meiosis resembles mitosis. Mammalian oocytes arrest constitutively at metaphase II in presence of aligned chromosomes, which is due to the activity of the cytostatic factor (CSF). The SAC has been identified in spermatogenesis and oogenesis, but gender-differences may contribute to sex-specific differential responses to aneugens. The age-related reduction in expression of components of the SAC in mammalian oocytes may act synergistically with spindle and other cell organelles’ dysfunction, and a partial loss of cohesion between sister chromatids to predispose oocytes to errors in chromosome segregation. This might affect dose–response to aneugens. In view of the tendency to have children at advanced maternal ages it appears relevant to pursue studies on consequences of ageing on the susceptibility of human oocytes to the induction of meiotic error by aneugens and establish models to assess risks to human health by environmental exposures. [Copyright &y& Elsevier]
Copyright of Mutation Research - Genetic Toxicology & Environmental Mutagenesis is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Spindle formation, chromosome segregation and the spindle checkpoint in mammalian oocytes and susceptibility to meiotic error
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  Data: <searchLink fieldCode="AR" term="%22Vogt%2C+E%2E%22">Vogt, E.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Kirsch-Volders%2C+M%2E%22">Kirsch-Volders, M.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Parry%2C+J%2E%22">Parry, J.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Eichenlaub-Ritter%2C+U%2E%22">Eichenlaub-Ritter, U.</searchLink><relatesTo>1</relatesTo><i> EiRi@uni-bielefeld.de</i>
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  Data: <searchLink fieldCode="JN" term="%22Mutation+Research+-+Genetic+Toxicology+%26+Environmental+Mutagenesis%22">Mutation Research - Genetic Toxicology & Environmental Mutagenesis</searchLink>. Mar2008, Vol. 651 Issue 1/2, p14-29. 16p.
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  Data: *<searchLink fieldCode="DE" term="%22Genetics%22">Genetics</searchLink><br /><searchLink fieldCode="DE" term="%22Spindle+apparatus%22">Spindle apparatus</searchLink><br /><searchLink fieldCode="DE" term="%22Chromosomes%22">Chromosomes</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+mutation%22">Genetic mutation</searchLink>
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  Data: Abstract: The spindle assembly checkpoint (SAC) monitors attachment to microtubules and tension on chromosomes in mitosis and meiosis. It represents a surveillance mechanism that halts cells in M-phase in the presence of unattached chromosomes, associated with accumulation of checkpoint components, in particular, Mad2, at the kinetochores. A complex between the anaphase promoting factor/cylosome (APC/C), its accessory protein Cdc20 and proteins of the SAC renders APC/C inactive, usually until all chromosomes are properly assembled at the spindle equator (chromosome congression) and under tension from spindle fibres. Upon release from the SAC the APC/C can target proteins like cyclin B and securin for degradation by the proteasome. Securin degradation causes activation of separase proteolytic enzyme, and in mitosis cleavage of cohesin proteins at the centromeres and arms of sister chromatids. In meiosis I only the cohesin proteins at the sister chromatid arms are cleaved. This requires meiosis specific components and tight regulation by kinase and phosphatase activities. There is no S-phase between meiotic divisions. Second meiosis resembles mitosis. Mammalian oocytes arrest constitutively at metaphase II in presence of aligned chromosomes, which is due to the activity of the cytostatic factor (CSF). The SAC has been identified in spermatogenesis and oogenesis, but gender-differences may contribute to sex-specific differential responses to aneugens. The age-related reduction in expression of components of the SAC in mammalian oocytes may act synergistically with spindle and other cell organelles’ dysfunction, and a partial loss of cohesion between sister chromatids to predispose oocytes to errors in chromosome segregation. This might affect dose–response to aneugens. In view of the tendency to have children at advanced maternal ages it appears relevant to pursue studies on consequences of ageing on the susceptibility of human oocytes to the induction of meiotic error by aneugens and establish models to assess risks to human health by environmental exposures. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Mutation Research - Genetic Toxicology & Environmental Mutagenesis is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1016/j.mrgentox.2007.10.015
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        Text: English
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      – SubjectFull: Chromosomes
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      – SubjectFull: Genetic mutation
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      – TitleFull: Spindle formation, chromosome segregation and the spindle checkpoint in mammalian oocytes and susceptibility to meiotic error
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              Text: Mar2008
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              Y: 2008
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