BACKGROUNDIn prokaryotic organisms, the mechanism responsible for the accurate partition of newly replicated chromosomes into daughter cells is incompletely understood. Segregation of the replication terminus of the circular prokaryotic chromosome poses special problems that have not previously been addressed. The aim of this study was to investigate the roles of several protein components (MreB, MreC, and MreD) of the prokaryotic cytoskeleton for the faithful transmission of the chromosomal terminus into daughter cells.

METHODSStrain LQ1 (mreB::cat), LQ2 (mreC::cat), and LQ3 (mreD::cat) were constructed using the Red recombination system. LQ11/pLAU53, LQ12/pLAU53, LQ13/pLAU53, LQ14/pLAU53, and LQ15/pLAU53 strains were generated by P1transduction of (tetO) 240 -Gm and (lacO) 240 -Km cassettes from strains IL2 and IL29. Fluorescence microscopy was performed to observe localization pattern of fluorescently-labeled origin and terminus foci in wild-type and mutant cells. SOS induction was monitored as gfp fluorescence from PsulA-gfp in log phase cells grown in Luria-Bertani medium at 37°C by measurement of emission at 525 nm with excitation at 470 nm in a microplate fluorescence reader.

RESULTSMutational deletion of the mreB, mreC, or mreD genes was associated with selective loss of the terminus region in approximately 40% of the cells within growing cultures. This was accompanied by significant induction of the SOS DNA damage response, suggesting that deletion of terminus sequences may have occurred by chromosomal cleavage, presumably caused by ingrowth of the division septum prior to segregation of the replicated terminal.

CONCLUSIONSThese results imply a role for the MreBCD cytoskeleton in the resolution of the final products of terminus replication and/or in the specific movement of newly replicated termini away from midcell prior to completion of septal ingrowth. This would identify a previously unrecognized stage in the overall process of chromosome segregation.

The synaptonemal complex (SC) is a meiosis-specific proteinaceous macromolecular structure that assembles between paired homologous chromosomes during meiosis in various eukaryotes. The SC has a highly conserved ultrastructure and plays critical roles in controlling multiple steps in meiotic recombination and crossover formation, ensuring accurate meiotic chromosome segregation. Recent studies in different organisms, facilitated by advances in super-resolution microscopy, have provided insights into the macromolecular structure of the SC, including the internal organization of the meiotic chromosome axis and SC central region, the regulatory pathways that control SC assembly and dynamics, and the biological functions exerted by the SC and its substructures. This review summarizes recent discoveries about how the SC is organized and regulated that help to explain the biological functions associated with this meiosis-specific structure.
Animals ; Chromosome Segregation ; Meiosis/physiology* ; Synaptonemal Complex/physiology*

The chromosomal aneuploidy in oocytes is one of main causes of abortion and neonatal birth defects.It is mainly due to the premature separation of sister chromatid caused by the loss of Cohesin protein complex and the non-disjunction sister chromatids caused by abnormal microtubule dynamics aneuploidy.As a pathway of protein post-translational modification,SUMO modification(or SUMOylation)involves many physiological regulation processes including cell proliferation,differentiation,apoptosis,and cycle regulation.In the oocytes,SUMOylation can regulate the localization of Cohesin protein complex on the chromosome to affect the chromosomal aneuploidy in oocytes caused by premature separation of sister chromatid.On the other hand,SUMOylation can regulate the microtubule dynamics to affect the chromosomal aneuploidy in oocytes caused by non-disjunction sister chromatids.Therefore,SUMOylation plays an important role in regulating the chromosomal aneuploidy of oocytes;the exact mechanisms via which the SUMOylated substrates affect aneuploidy in oocytes remain unclear.This articles reviews the roles of SUMOylation in premature separation and non-isolated chromatid aneuploidy in oocyte from the effects of SUMOylationon Cohesin protein complex and microtubule dynamics.
Aneuploidy ; Cell Cycle Proteins ; Chromatids ; Chromosomal Proteins, Non-Histone ; Chromosome Segregation ; Humans ; Microtubules ; Oocytes ; cytology ; Sumoylation

Aurora kinase A (AURKA),a family member of aurora kinases,is involved in mitotic entry,maturation and separation of centrosome,assembly and stabilization of bipolar spindle,and condensation and separation of chromosome.Studies have demonstrated that AURKA plays a similar role in meiosis,while the specific mechanism and the similarities and differences in its role between meiosis and mitosis remain unclear.Therefore,we reviewed the studies about the localization and activation of AURKA in oocyte meiosis,and compared the role of AURKA in regulating spindle formation,activating spindle assembly checkpoint,and correcting the kinetochore-microtubule attachment between the meiosis of oocytes and the mitosis of somatic cells.This review will lay a theoretical foundation for revealing the mechanism of AURKA in the regulation of cell division and for the clinical research related to cancer and reproduction.
Aurora Kinase A/genetics* ; Cell Cycle Proteins/genetics* ; Chromosome Segregation ; Humans ; Meiosis ; Oocytes

Repairing DNA double-strand breaks (DSBs) with homologous chromosomes as templates is the hallmark of meiosis. The critical outcome of meiotic homologous recombination is crossovers, which ensure faithful chromosome segregation and promote genetic diversity of progenies. Crossover patterns are tightly controlled and exhibit three characteristics: obligatory crossover, crossover interference, and crossover homeostasis. Aberrant crossover patterns are the leading cause of infertility, miscarriage, and congenital disease. Crossover recombination occurs in the context of meiotic chromosomes, and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally. Meiotic chromosomes are organized in a loop-axis architecture. Diverse evidence shows that chromosome axis length determines crossover frequency. Interestingly, short chromosomes show different crossover patterns compared to long chromosomes. A high frequency of human embryos are aneuploid, primarily derived from female meiosis errors. Dramatically increased aneuploidy in older women is the well-known "maternal age effect." However, a high frequency of aneuploidy also occurs in young women, derived from crossover maturation inefficiency in human females. In addition, frequency of human aneuploidy also shows other age-dependent alterations. Here, current advances in the understanding of these issues are reviewed, regulation of crossover patterns by meiotic chromosomes are discussed, and issues that remain to be investigated are suggested.
Cell Division/physiology* ; Chromosome Segregation/physiology* ; Humans ; Meiosis/genetics* ; Recombination, Genetic

Programmed DNA double-strand breaks (DSBs) are necessary for meiosis in mammals. A sufficient number of DSBs ensure the normal pairing/synapsis of homologous chromosomes. Abnormal DSB repair undermines meiosis, leading to sterility in mammals. The DSBs that initiate recombination are repaired as crossovers and noncrossovers, and crossovers are required for correct chromosome separation. Thus, the placement, timing, and frequency of crossover formation must be tightly controlled. Importantly, mutations in many genes related to the formation and repair of DSB result in infertility in humans. These mutations cause nonobstructive azoospermia in men, premature ovarian insufficiency and ovarian dysgenesis in women. Here, we have illustrated the formation and repair of DSB in mammals, summarized major factors influencing the formation of DSB and the theories of crossover regulation.
Animals ; Chromosome Segregation ; DNA Breaks, Double-Stranded ; DNA Repair/physiology* ; Humans ; Mammals/genetics*

Varying degrees of necrozoospermia are common findings in cases of male sub-fertility; however, it is rare to find persistent and 100 % necrozoospermia. A case of persistent 100 % necrozoospermia was presented in this paper, where aneuploidy analysis was carried out on sperm. No known associations like thyrotoxicosis, genital infection, spinal injury and diabetes were found. Sperm fluorescent in situ hybridization (FISH) was carried out to evaluate sperm aneuploidy for chromosome 1, 9, 12, 13, 16, 18, 21, X and Y and did not show any excess of aneuploidy over controls. To the best of our knowledge, this is the first attempt on meiotic segregation analysis on 100 % necrozoospermic patients.
Adult ; Aneuploidy ; Chromosome Mapping ; Chromosome Segregation ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Meiosis ; Necrosis ; Oligospermia ; genetics ; pathology ; Spermatozoa ; pathology

OBJECTIVE: Previously, we found that oocyte specific homeobox (Obox) 4 plays significant role in completion of meiosis specifically at meiosis I-meiosis II (MI-MII) transition. The purpose of this study was to determine the mechanism of action of Obox4 in oocyte maturation by evaluating downstream signal networking. METHODS: The Obox4 dsRNA was prepared by in vitro transcription and microinjected into the cytoplasm of germinal vesicle oocytes followed by in vitro maturation in the presence or absence of 0.2 mM 3-isobutyl-1-metyl-xanthine. Total RNA was extracted from 200 oocytes of each group using a PicoPure RNA isolation kit then amplified two-rounds. The probe hybridization and data analysis were used by Affymetrix GeneChip(R) Mouse Genome 430 2.0 array and GenPlex 3.0 (ISTECH, Korea) software, respectively. RESULTS: Total 424 genes were up (n=80) and down (n=344) regulated after Obox4 RNA interference (RNAi). Genes mainly related to metabolic pathways and mitogen-activated protein kinase (MAPK) signaling pathway was changed. Among the protein kinase C (PKC) isoforms, PKC-alpha, beta, gamma were down-regulated and especially the MAPK signaling pathway PKC-gamma was dramatically decreased by Obox4 RNAi. In the cell cycle pathway, we evaluated the expression of genes involved in regulation of chromosome separation, and found that these genes were down-regulated. It may cause the aberrant chromosome segregation during MI-MII transition. CONCLUSION: From the results of this study, it is concluded that Obox4 is important upstream regulator of the PKC and anaphase-promoting complex action for maintaining intact germinal vesicle.
Animals ; Cell Cycle ; Chimera ; Chromosome Segregation ; Cytoplasm ; Gene Expression ; Genes, Homeobox ; Genome ; Meiosis ; Metabolic Networks and Pathways ; Mice ; Microarray Analysis ; Oocytes ; Protein Isoforms ; Protein Kinase C ; Protein Kinases ; RNA ; RNA Interference ; Statistics as Topic ; Ubiquitin-Protein Ligase Complexes

BubR1 gene is a homologue of the mitotic checkpoint gene Mad3 in budding yeast which is highly conserved in mammalian. BubR1 protein is a key component mediating spindle assembly checkpoint activation. BubR1 safeguards accurate chromosome segregation during cell division by monitoring kinetochore-microtubule attachments and kinetochore tension. There is a dose-dependent effect between the level of BubR1 expression and the function of spindle assembly checkpoint. BubR1-deficient would lead to mitotic progression with compromised spindle assembly checkpoint because cells become progressively aneuploid. Recently, it has been reported that BubR1 also plays important roles in meiotic, DNA damage response, cancer, infertility, and early aging. This review briefly summarizes the current progresses in studies of BubR1 function.
Cell Cycle Proteins ; genetics ; metabolism ; physiology ; Chromosome Segregation ; genetics ; physiology ; Kinetochores ; metabolism ; physiology ; Mitosis ; genetics ; physiology ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; physiology ; Saccharomycetales ; genetics ; physiology ; Spindle Apparatus ; genetics ; metabolism ; physiology

Miller-Dieker syndrome involves a severe type of lissencephaly, which is caused by defects in the lissencephaly gene (LIS1). We report the case of a female infant with der(17)t(12;17)(q24.33;p13.3)pat caused by an unbalanced segregation of the parental balanced translocation of 17p with other chromosomes. The proband presented with facial dysmorphism, arthrogryposis, and intrauterine growth retardation. Most cases of Miller-Dieker syndrome have a de novo deletion involving 17p13.3. When Miller-Dieker syndrome is caused by an unbalanced translocation, mild-to-severe phenotypes occur according to the extension of the involved partner chromosome. However, a pure partial monosomy derived from a paternal balanced translocation is relatively rare. In this case, the submicroscopic cryptic deletion in the proband was initially elucidated by FISH, and karyotype analysis did not reveal additional chromosome abnormalities such as translocation. However, a family history of recurrent pregnancy abnormalities strongly suggested familial translocation. Sequential G-banding and FISH analysis of the father's chromosomes showed that the segment of 17p13.3-->pter was attached to the 12qter. Thus, we report a case that showed resemblance to the findings in cases of a nearly pure 17p deletion, derived from t(12;17), and delineated by whole genome array comparative genomic hybridization (CGH). If such cases are incorrectly diagnosed as Miller-Dieker syndrome caused by de novo 17p13.3 deletion, the resultant improper genetic counseling may make it difficult to exactly predict the potential risk of recurrent lissencephaly for successive pregnancies.
Abnormalities, Multiple/genetics ; Adult ; Brain/abnormalities ; Chromosome Banding ; Chromosome Segregation ; *Chromosomes, Human, Pair 12 ; *Chromosomes, Human, Pair 17 ; Classical Lissencephalies and Subcortical Band Heterotopias/*diagnosis ; Female ; Gene Deletion ; Humans ; In Situ Hybridization, Fluorescence ; Infant, Newborn ; Karyotyping ; Magnetic Resonance Imaging ; Male ; Phenotype ; Risk ; Translocation, Genetic