Article

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

University of Bielefeld, Faculty of Biology, Gene Technology/Microbiology, Bielefeld, Germany.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (impact factor: 2.85). 04/2008; 651(1-2):14-29. DOI:10.1016/j.mrgentox.2007.10.015 pp.14-29
Source: PubMed

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.

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    Wei Cui, Jie Zhang, Hua-Yu Lian, Hui-Li Wang, De-Qiang Miao, Chuan-Xin Zhang, Ming-Jiu Luo, Jing-He Tan
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    PLoS ONE 01/2012; 7(2):e32044. · 4.09 Impact Factor
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    Article: The multiple roles of Bub1 in chromosome segregation during mitosis and meiosis.
    Francesco Marchetti, Sundaresan Venkatachalam
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    ABSTRACT: Aneuploidy, any deviation from an exact multiple of the haploid number of chromosomes, is a common occurrence in cancer and represents the most frequent chromosomal disorder in newborns. Eukaryotes have evolved mechanisms to assure the fidelity of chromosome segregation during cell division that include a multiplicity of checks and controls. One of the main cell division control mechanisms is the spindle assembly checkpoint (SAC) that monitors the proper attachment of chromosomes to spindle fibers and prevents anaphase until all kinetochores are properly attached. The mammalian SAC is composed of at least 14 evolutionary-conserved proteins that work in a coordinated fashion to monitor the establishment of amphitelic attachment of all chromosomes before allowing cell division to occur. Among the SAC proteins, the budding uninhibited by benzimidazole protein 1 (Bub1), is a highly conserved protein of prominent importance for the proper functioning of the SAC. Studies have revealed many roles for Bub1 in both mitosis and meiosis, including the localization of other SAC proteins to the kinetochore, SAC signaling, metaphase congression and the protection of sister chromatid cohesion. Recent data show striking sex specific differences in the response of germ cells to alterations in Bub1 activity. Proper Bub1 functioning is particularly important during oogenesis in preventing the generation of aneuploid gametes that can have detrimental effects on the health status of the fetus and the newborn. These data suggest that Bub1 is a master regulator of SAC and chromosomal segregation in both mitosis and meiosis. Elucidating its many essential functions in regulating proper chromosome segregation can have important consequences for preventing tumorigenesis and developmental abnormalities.
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    PLoS ONE 01/2011; 6(11):e27143. · 4.09 Impact Factor

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Keywords

age-related reduction
 
checkpoint components
 
chromosome segregation
 
cyclin B
 
cytostatic factor
 
environmental exposures
 
halts cells
 
human health
 
human oocytes
 
mammalian oocytes
 
meiotic divisions
 
mitosis cleavage
 
phosphatase activities
 
predispose oocytes
 
requires meiosis specific components
 
Second meiosis
 
spindle assembly checkpoint
 
spindle equator
 
spindle fibres
 
surveillance mechanism
 

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