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1.
The separation of homologous chromosomes during meiosis in eukaryotes is the physical basis of Mendelian inheritance. The core of the meiotic process is a specialized nuclear division (meiosis I) in which homologs pair with each other, recombine, and then segregate from each other. The processes of chromosome alignment and pairing allow for homolog recognition. Reciprocal meiotic recombination ensures meiotic chromosome segregation by converting sister chromatid cohesion into mechanisms that hold homologous chromosomes together. Finally, the ability of sister kinetochores to orient to a single pole at metaphase I allows the separation of homologs to two different daughter cells. Failures to properly accomplish this elegant chromosome dance result in aneuploidy, a major cause of miscarriage and birth defects in human beings. 相似文献
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During meiosis, two chromosome segregation phases follow a single round of DNA replication. We identified factors required to establish this specialized cell cycle by examining meiotic chromosome segregation in a collection of yeast strains lacking all nonessential genes. This analysis revealed Sgo1, Chl4, and Iml3 to be important for retaining centromeric cohesin until the onset of anaphase II. Consistent with this role, Sgo1 localizes to centromeric regions but dissociates at the onset of anaphase II. The screen described here provides a comprehensive analysis of the genes required for the meiotic cell cycle and identifies three factors important for the stepwise loss of sister chromatid cohesion. 相似文献
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Janssen A van der Burg M Szuhai K Kops GJ Medema RH 《Science (New York, N.Y.)》2011,333(6051):1895-1898
Various types of chromosomal aberrations, including numerical (aneuploidy) and structural (e.g., translocations, deletions), are commonly found in human tumors and are linked to tumorigenesis. Aneuploidy is a direct consequence of chromosome segregation errors in mitosis, whereas structural aberrations are caused by improperly repaired DNA breaks. Here, we demonstrate that chromosome segregation errors can also result in structural chromosome aberrations. Chromosomes that missegregate are frequently damaged during cytokinesis, triggering a DNA double-strand break response in the respective daughter cells involving ATM, Chk2, and p53. We show that these double-strand breaks can lead to unbalanced translocations in the daughter cells. Our data show that segregation errors can cause translocations and provide insights into the role of whole-chromosome instability in tumorigenesis. 相似文献
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【目的】通过SCP3蛋白免疫荧光染色法,研究小鼠初级精母细胞减数分裂前期Ⅰ不同分裂相联会复合体的形态变化。【方法】从小鼠睾丸取曲细精管,用铺展法制片,对初级精母细胞SCP3蛋白进行免疫荧光染色,观察减数分裂前期Ⅰ不同分裂相联会复合体的形态变化。【结果】在细线期,可见短小、不连续而杂乱簇聚的SCP3蛋白片段;在偶线期,SCP3蛋白趋于明显,连续并呈线状,但没有形成完整的联会复合体;在粗线期,SCP3蛋白结构完整而清晰,小鼠初级精母细胞联会复合体共有20条,包括19条常染色体联会复合体和1条XY联会复合体;双线期,构成联会复合体的2条SCP3蛋白开始相互排斥而分离,导致联会复合体开始解体,但此时的二价体结构依然清晰可见。【结论】SCP3蛋白免疫荧光染色是研究减数分裂前期Ⅰ不同分裂相联会复合体形态变化的强有力工具。 相似文献
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We have identified a homolog of the mammalian p53 tumor suppressor protein in the nematode Caenorhabditis elegans that is expressed ubiquitously in embryos. The gene encoding this protein, cep-1, promotes DNA damage-induced apoptosis and is required for normal meiotic chromosome segregation in the germ line. Moreover, although somatic apoptosis is unaffected, cep-1 mutants show hypersensitivity to hypoxia-induced lethality and decreased longevity in response to starvation-induced stress. Overexpression of CEP-1 promotes widespread caspase-independent cell death, demonstrating the critical importance of regulating p53 function at appropriate levels. These findings show that C. elegans p53 mediates multiple stress responses in the soma, and mediates apoptosis and meiotic chromosome segregation in the germ line. 相似文献
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Reproductive cells that are destined to become sperm or egg undergo meiotic division during which the chromosome number is halved. As Sluder and McCollum explain in their Perspective, new findings (Shonn et al.) in yeast show that there is a spindle checkpoint that operates during meiosis to ensure that an equal number of replicated chromosomes arrives at each pole of the cell. One of the components of this meiotic spindle checkpoint turns out to be Mad2, which gives the signal to halt meiosis if it looks like unequal chromosome segregation is taking place. 相似文献
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Meiosis is a specialized cell division in which two chromosome segregation phases follow a single DNA replication phase. The budding yeast Polo-like kinase Cdc5 was found to be instrumental in establishing the meiosis I chromosome segregation program. Cdc5 was required to phosphorylate and remove meiotic cohesin from chromosomes. Furthermore, in the absence of CDC5 kinetochores were bioriented during meiosis I, and Mam1, a protein essential for coorientation, failed to associate with kinetochores. Thus, sister-kinetochore coorientation and chromosome segregation during meiosis I are coupled through their dependence on CDC5. 相似文献
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Most organisms rely on interhomolog crossovers (COs) to ensure proper meiotic chromosome segregation but make few COs per chromosome pair. By monitoring repair events at a defined double-strand break (DSB) site during Caenorhabditis elegans meiosis, we reveal mechanisms that ensure formation of the obligate CO while limiting CO number. We find that CO is the preferred DSB repair outcome in the absence of inhibitory effects of other (nascent) recombination events. Thus, a single DSB per chromosome pair is largely sufficient to ensure CO formation. Further, we show that access to the homolog as a repair template is regulated, shutting down simultaneously for both CO and noncrossover (NCO) pathways. We propose that regulation of interhomolog access limits CO number and contributes to CO interference. 相似文献
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细胞松弛素B对牛卵母细胞体外成熟过程中微管、微丝及染色体的影响 总被引：1，自引：0，他引：1
细胞松弛素B(Cytochalasin B,CB)是一种抑制微丝聚合的药物,能抑制微丝的组装从而阻止胞质分裂和极体排放,是研究细胞分裂器形成与变化的重要药物。在牛卵母细胞体外成熟培养过程中加入7.5 μg/mL的CB进行处理,分析CB对减数分裂过程中细胞骨架形态、染色体的排列与分离等方面的影响。结果显示,CB处理后卵母细胞第一极体的排放受到了抑制,染色体的排列和分离受到了影响,出现了同源染色体分离不完全或分离不均匀及分离后又聚在一起等异常情况,形成许多二倍体卵母细胞;纺锤体微管的形态发生了变化,出现了两个纺锤体、巨大纺锤体和多极纺锤体等异常结构;微丝的正常分布受到了影响,染色体周围没有或少有微丝分布,皮质下的微丝分布也变得少而不均匀;这说明微丝与微管在减数分裂过程中是协同作用的,CB通过影响微丝的动态变化,改变了纺锤体微管的形态结构,最终抑制了极体的排放。 相似文献
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Doubled haploid (DH) breeding technology, which relies on haploid genome doubling, is widely used in commercial maize breeding. Spontaneous haploid genome doubling (SHGD), a more simplified and straightforward method, is gaining popularity among maize breeders. However, the cytological mechanism of SHGD remains unclear. This study crossed inbred lines RL36 and RL7, which have differing SHGD abilities, with inducer line YHI-1 to obtain haploid kernels. The meiotic processes of pollen mother cells (PMCs) in the haploid plants were compared with diploid controls. The results suggested that three main pathways, the early doubling of haploid PMCs, the first meiotic metaphase chromosomal segregation distortion, and anomaly of the second meiosis, are responsible for SHGD. Furthermore, flow cytometry analysis of ploidy levels in leaves and PMCs from haploids and diploid controls revealed that somatic cell chromosome doubling and germ cell chromosome doubling are independent processes. These findings provide a foundation for further studies on the underlying mechanism of SHGD, aiding the application of DH technology in maize breeding practices. 相似文献
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Antisense RNA directed against the 3' noncoding region prevents dormant mRNA activation in mouse oocytes 总被引：22，自引：0，他引：22
S Strickland J Huarte D Belin A Vassalli R J Rickles J D Vassalli 《Science (New York, N.Y.)》1988,241(4866):680-684
Primary mouse oocytes contain untranslated stable messenger RNA for tissue plasminogen activator (t-PA). During meiotic maturation, this maternal mRNA undergoes a 3'-polyadenylation, is translated, and is degraded. Injections of maturing oocytes with different antisense RNA's complementary to both coding and noncoding portions of t-PA mRNA all selectively blocked t-PA synthesis. RNA blot analysis of t-PA mRNA in injected, matured oocytes suggested a cleavage of the RNA.RNA hybrid region, yielding a stable 5' portion, and an unstable 3' portion. In primary oocytes, the 3' noncoding region was susceptible to cleavage, while the other portions of the mRNA were blocked from hybrid formation until maturation occurred. Injection of antisense RNA complementary to 103 nucleotides of its extreme 3' untranslated region was sufficient to prevent the polyadenylation, translational activation, and destabilization of t-PA mRNA. These results demonstrate a critical role for the 3' noncoding region of a dormant mRNA in its translational recruitment during meiotic maturation of mouse oocytes. 相似文献
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Pawlowski WP Golubovskaya IN Timofejeva L Meeley RB Sheridan WF Cande WZ 《Science (New York, N.Y.)》2004,303(5654):89-92
Pairing, synapsis, and recombination are prerequisites for accurate chromosome segregation in meiosis. The phs1 gene in maize is required for pairing to occur between homologous chromosomes. In the phs1 mutant, homologous chromosome synapsis is completely replaced by synapsis between nonhomologous partners. The phs1 gene is also required for installation of the meiotic recombination machinery on chromosomes, as the mutant almost completely lacks chromosomal foci of the recombination protein RAD51. Thus, in the phs1 mutant, synapsis is uncoupled from recombination and pairing. The protein encoded by the phs1 gene likely acts in a multistep process to coordinate pairing, recombination, and synapsis. 相似文献
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Lorenz A Osman F Sun W Nandi S Steinacher R Whitby MC 《Science (New York, N.Y.)》2012,336(6088):1585-1588
The formation of healthy gametes depends on programmed DNA double-strand breaks (DSBs), which are each repaired as a crossover (CO) or non-crossover (NCO) from a homologous template. Although most of these DSBs are repaired without giving COs, little is known about the genetic requirements of NCO-specific recombination. We show that Fml1, the Fanconi anemia complementation group M (FANCM)-ortholog of Schizosaccharomyces pombe, directs the formation of NCOs during meiosis in competition with the Mus81-dependent pro-CO pathway. We also define the Rad51/Dmc1-mediator Swi5-Sfr1 as a major determinant in biasing the recombination process in favor of Mus81, to ensure the appropriate amount of COs to guide meiotic chromosome segregation. The conservation of these proteins from yeast to humans suggests that this interplay may be a general feature of meiotic recombination. 相似文献
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Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes 总被引：3，自引：0，他引：3
Granulosa cells of mammalian Graafian follicles maintain oocytes in meiotic arrest, which prevents their precocious maturation. We show that mouse mural granulosa cells, which line the follicle wall, express natriuretic peptide precursor type C (Nppc) messenger RNA (mRNA), whereas cumulus cells surrounding oocytes express mRNA of the NPPC receptor NPR2, a guanylyl cyclase. NPPC increased cGMP levels in cumulus cells and oocytes and inhibited meiotic resumption in vitro. Meiotic arrest was not sustained in most Graafian follicles of Nppc or Npr2 mutant mice, and meiosis resumed precociously. Oocyte-derived paracrine factors promoted cumulus cell expression of Npr2 mRNA. Therefore, the granulosa cell ligand NPPC and its receptor NPR2 in cumulus cells prevent precocious meiotic maturation, which is critical for maturation and ovulation synchrony and for normal female fertility. 相似文献
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为探讨和比较磷酸二酯酶(PDE)3、4和5对小鼠卵母细胞体外自发成熟的影响,将小鼠卵丘卵母细胞复合体(COCs)和裸卵(DOs)分别培养在含有或不含有PDE 3、4和5特异性抑制剂的M-199培养液中。结果表明:PDE3的特异性抑制剂cilostamide和PDE5的特异性抑制剂zaprinast均能显著抑制小鼠COCs和DOs的自发成熟,且其抑制效应不随培养时间的延长而减弱,但却是可逆的;而PDE4的特异性抑制剂rolipram对小鼠COCs和DOs没有影响。上述结果提示,不同亚型的PDE在小鼠卵母细胞减数分裂过程中具有不同的调节作用。 相似文献
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In mammals, fertilization typically involves the ovulation of one or a few eggs at one end of the female reproductive tract and the entry of millions of sperm at the other. Given this disparity in numbers, it might be expected that the more precious commodity-eggs-would be subject to more stringent quality-control mechanisms. However, information from engineered mutations of meiotic genes suggests just the opposite. Specifically, the available mutants demonstrate striking sexual dimorphism in response to meiotic disruption; for example, faced with adversity, male meiosis grinds to a halt, whereas female meiosis soldiers on. This female "robustness" comes with a cost, however, because aneuploidy appears to be increased in the resultant oocytes. 相似文献
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We report the discovery of a checkpoint that monitors synapsis between homologous chromosomes to ensure accurate meiotic segregation. Oocytes containing unsynapsed chromosomes selectively undergo apoptosis even if a germline DNA damage checkpoint is inactivated. This culling mechanism is specifically activated by unsynapsed pairing centers, cis-acting chromosome sites that are also required to promote synapsis in Caenorhabditis elegans. Apoptosis due to synaptic failure also requires the C. elegans homolog of PCH2, a budding yeast pachytene checkpoint gene, which suggests that this surveillance mechanism is widely conserved. 相似文献
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