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*

Cell Nucleus Division ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Leiomyoma ; metabolism ; pathology ; physiopathology ; Smooth Muscle Tumor ; metabolism ; pathology ; physiopathology ; Uterine Neoplasms ; metabolism ; pathology ; physiopathology

Oral cancer take up 2-6% of all carcinomas and squamous cell carcinoma, which is the most common type in oral cancer, has a poor prognosis due to its high metastasis and recurrence rates. In treating oral cancer, chemotherapy to the primary, metastasized and recurrent lesion is a very important and useful treatment, even though its widespread usage is limited due to high general toxicity and local toxicity to other organs. Taxol, a microtubule stabilizing agent, is an anticancer drug that induces cell apoptosis by inhibiting depolymerization of microtubules in between the metaphase and anaphase of the cell mitosis. Recently, its effectiveness and mechanism on various tumor has been reported. However, not much research has been done on the application of Taxol to oral squamous cell carcinoma. Cyclosporin A, which is an immunosuppressant, is being used on cancers and when co-administered with Taxol, effectiveness of Taxol is enhanced by inhibition of Taxol induced multidrug resistance. In this study, Cyclosporin A with different concentration of Taxol was co-administered to HN22, the oral squamous cell carcinomacell line. To observe the cell apoptosis and the mechanisms that take part in this process, mortality evaluation of tumor cell using wortmannin, c-DNA microarray, RT-PCR analysis, cytometry analysis and western blotting were used, and based upon the observation on the effect and mechanism of the agent, the following results were obtained: 1. The HN22 cell line viability was lowest when 100micrometer of Wortmannin and 5microgram/ml of Taxol were co-administered, showing that Taxol participates in P13K-AKT1 pathway. 2. In c-DNA microarray, where 1microgram/ml of cyclosporine A and 3mg/ml of Taxol were co-administered, no up regulation of AKT1, PTEN and BAD c-DNA that participate in cell apoptosis was observed. 3. When 1microgram/ml of Cyclosporin A was applied alone to HN22 cell line,no difference was found in AKT1, PTEN and BAD mRNA expression. 4. Increased AKT1, mRNA expression was observed when 3microgram/ml of Taxol was applied alone to HN22 cell line. 5. When 1microgram/ml of Cyclosporin A and Taxol (3microgram/ml and 5microgram/ml) were co-administered to HN22 cell line, PTEN mRNA expression increased, whereas AKT1 and BAD mRNA decreased. 6. As a result of cytometry analysis, in the group of Cyclosporin A(1microgram/ml) and Taxol(3microgram/ml) co-administration, increased Annxin V was observed, which shows that apoptosis occurred by deformation of plasma membrane. However, no significant difference was observed with varying concentration. 7. In western blot analysis, no caspase 3 was observed in the group of Cyclosporin A(1microgram/ml) and Taxol(3microgram/ml) co-administration. From the results of this study, it can be concluded that synergistic effect can be observed in combination therapy of Taxol and Cyclosporin A on oral squamous cell carcinoma cell line, where decreased activity of the cell line was observed. This resulted in decreased AKT1 and BAD mRNA and increased PTEN mRNA expression and when wortmannin and Taxol were co-administered, the viability decreased which confirms that Taxol decreases the viability of tumor cell line. Hence, when Taxol and cyclosporine A are co-administered, it can be assumed that cell apoptosis occurs through AKt1 pathway.
Anaphase ; Apoptosis ; Blotting, Western ; Carcinoma, Squamous Cell* ; Caspase 3 ; Cell Line* ; Cell Line, Tumor ; Cell Membrane ; Cyclosporine* ; Drug Resistance, Multiple ; Drug Therapy ; Metaphase ; Microtubules ; Mitosis ; Mortality ; Mouth Neoplasms ; Neoplasm Metastasis ; Oligonucleotide Array Sequence Analysis ; Paclitaxel* ; Prognosis ; Recurrence ; RNA, Messenger ; Up-Regulation

Sec13p has been known as an endoplasmic reticulum-Golgi transport protein. Recently, it has also been shown to be required for the formation of septation in the fission yeast Schizosaccharomyces pombe. In the present study, we focused on the role of a human homolog of Saccharomyces cerevisiae SEC13, Sec13 protein during mitosis in U2OS cells. We found that the expression of Sec13 was constant throughout the cell cycle, and localized to the kinetochores at metaphase during mitosis. By using green fluorescent protein technology, we observed that Sec13 is required for evasion of mitotic arrest in response to spindle damage, leading to G1-like phase and apoptotic cell death. In addition, cells expressing exogenous Sec13 showed giant nuclei compared to endogenous ones in the absence of nocodazole. These results demonstrate that Sec13 is involved in the regulation of the metaphase/anaphase transition and may be functionally associated with mitotic machinery to maintain genomic stability during mitosis.
Anaphase ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor/drug effects/metabolism/pathology ; *G1 Phase ; *Genomic Instability ; Green Fluorescent Proteins/metabolism ; Humans ; Kinetochores/metabolism ; Membrane Proteins/*genetics/metabolism ; Metaphase ; Mitosis/*physiology ; *Mitotic Spindle Apparatus ; Nocodazole/pharmacology ; Osteosarcoma/genetics/metabolism/pathology ; Research Support, Non-U.S. Gov't

OBJECTIVETo investigate the tumorigenic mechanisms of human leukemia cell line HL60-n in nude mice.

METHODSDifferent clone strains of HL60-n cells were established by limited dilution and their biological features were compared with parental HL-60 cells.

RESULTSThe colony yields in soft agar, especially the large colony yields of the high tumorigenic clone strains HL60-n/A, HL60-n/B were significantly higher than that of the HL-60 cells (P < 0.01). There was no significant difference between the low tumorigenic clone strains HL60-n/E, HL60-n/F and the HL-60 cells. Ultrastructurally, the nucleus was highly abnormal, the euchromatic element of nuclear chromatin increased, the heterochromatin sparse, and the microfilaments in cytoplasm increased and disarranged in the high tumorigenic cells as compared with HL-60 cells. Cell cycle analysis by flow cytometer showed higher S phase fractions in the high tumorigenic cells. The killing activities of NK cells to the high tumorigenic clone strains were significant lower than to the contrast (P < 0.01). The histopathological features produced by the low tumorigenic leukemia cells showed that there were many inflammatory cells infiltrated, the majority of them were lymphocytes, and many tumor cells were killed especially in vessel abundant areas. By contrast, there were few inflammatory cells infiltrated in the tumors produced by the high tumorigenic cell strains.

CONCLUSIONThe mechanism of the high tumorigenic activity of the HL60-n cell line involved higher colony yields in soft agar, higher S phase fraction, decreased susceptibility to NK cell killing, and the inhibition of the host immunity.

Animals ; Carcinogenicity Tests ; Cell Division ; physiology ; Cell Nucleus ; pathology ; ultrastructure ; Disease Models, Animal ; HL-60 Cells ; Humans ; Killer Cells, Natural ; cytology ; immunology ; Leukemia ; pathology ; physiopathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; pathology ; Tumor Stem Cell Assay

Animals ; Biomarkers, Tumor ; genetics ; metabolism ; Cell Nucleus Division ; Cystadenocarcinoma, Serous ; classification ; genetics ; metabolism ; pathology ; Female ; Humans ; Mutation ; Neoplasm Grading ; Ovarian Neoplasms ; classification ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins B-raf ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism

CUE domain-containing 2 (CUEDC2) is a protein involved in the regulation of the cell cycle, inflammation, and tumorigenesis and is highly expressed in many types of tumors. CUEDC2 is phosphorylated by Cdk1 during mitosis and promotes the release of anaphase-promoting complex or cyclosome (APC/C) from checkpoint inhibition. CUEDC2 is also known to interact with IkB kinase α (IKKα) and IKKβ and has an inhibitory role in the activation of transcription factor nuclear factor-κB. Moreover, CUEDC2 plays an important role in downregulating the expression of hormone receptors estrogen receptor-α and progesterone receptor, thereby impairing the responsiveness of breast cancer to endocrine therapies. In this review, current knowledge on the multi-functions of CUEDC2 in normal processes and tumorigenesis are discussed and summarized.
Anaphase-Promoting Complex-Cyclosome ; Breast Neoplasms ; pathology ; Carrier Proteins ; metabolism ; Cell Cycle Proteins ; metabolism ; Cell Transformation, Neoplastic ; pathology ; Estrogen Receptor alpha ; metabolism ; Female ; Humans ; I-kappa B Kinase ; metabolism ; Inflammation ; pathology ; M Phase Cell Cycle Checkpoints ; Membrane Proteins ; metabolism ; Mitosis ; NF-kappa B p50 Subunit ; metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases ; metabolism ; Signal Transduction ; Ubiquitin-Protein Ligase Complexes ; metabolism ; Ubiquitination

The aim of the present study is to observe the dynamic changes of γ-tubulin in mouse somatic nuclear transferred (SCNT) embryos. The γ-tubulin was detected and analyzed in the enucleated oocyte and SCNT embryos by immunofluorescence and laser confocal microscopy. The results showed that γ-tubulin distributed in the cortex of the enucleated MII oocytes, and decreased in this area during the activation of oocytes. Meanwhile cytoplasmic asters appeared, but there was no spindle formed. Spindle formation could be observed in the enucleated oocytes which were injected with cumulus cells and activated by SrCl2. The spots-like γ-tubulin signals spread between chromosomes at the prophase, and the signals arrayed with spindle or aggregated at two poles of the spindle at the early metaphase. Furthermore, γ-tubulin signals were localized between the segregated sister chromatids at anaphase or telophase. Some reconstructed embryos exhibited advanced activation, showing abnormal spindles and aberrant distribution of γ-tubulin and chromosomes. Two spindles would be formed when the cumulus cell was injected into an intact oocyte, and the distribution of γ-tubulin was similar to that of the normal SCNT. Moreover, advanced activation also occurred in this case and formed either two small spindles or one big barrel-shaped spindle. These results suggest that γ-tubulin plays a pivotal role in spindle assembling in mouse SCNT embryos. The reconstructed oocytes were easily to be activated, and aberrant distribution of γ-tubulin is associated with formation of abnormal spindles and chromosome misalignment.
Animals ; Embryo, Mammalian ; metabolism ; Fluorescent Antibody Technique ; Metaphase ; Mice ; Microscopy, Confocal ; Nuclear Transfer Techniques ; Oocytes ; cytology ; Spindle Apparatus ; metabolism ; Telophase ; Tubulin ; metabolism

An increasing number of monopartite begomoviruses are being identified that a satellite molecule (DNAbeta) is required to induce typical symptoms in host plants. DNAbeta encodes a single gene (termed betaC1) encoded in the complementary-sense. We have produced transgenic Nicotiana benthamiana and N. tabacum plants expressing the betaC1 gene of a DNAbeta associated with Tomato yellow leaf curl China virus (TYLCCNV), under the control of the Cauliflower mosaic virus 35S promoter. Transgenic plants expressing betaC1 showed severe developmental abnormalities in both species. Microscopic analysis of sections of both transgenic and non-transgenic N. tabacum leaves showed abnormal outgrowths of transgenic N. tabacum to be due to disorganized cell division (hyperplasia) of spongy and palisade parenchyma. Immuno-gold labeling of sections with a polyclonal antibody against the betaC1 protein showed that the betaC1 protein accumulated in the nuclei of cells. The possible biological function of the betaC1 protein was discussed.
Cell Division ; physiology ; Cell Nucleus ; genetics ; metabolism ; ultrastructure ; Cells, Cultured ; DNA, Viral ; genetics ; Geminiviridae ; genetics ; Plant Diseases ; genetics ; virology ; Plant Leaves ; cytology ; genetics ; growth & development ; metabolism ; Plants, Genetically Modified ; growth & development ; metabolism ; Recombinant Proteins ; metabolism ; Tobacco ; cytology ; growth & development ; metabolism ; ultrastructure ; Viral Proteins ; genetics ; metabolism

OBJECTIVETo analyze defective homologous chromosomal recombination in Han Chinese azoospermic patients.

METHODSTesticular biopsy samples from 7 healthy controls and 7 Han Chinese azoospermic patients including 2 obstructive azoospermia (OA group) and 5 non-obstructive azoospermia (NOA group) were analyzed. Immunofluorescence staining was performed to categorize early stage cells at meiosis prophase and to analyze chromosome pairing and recombination of pachytene spermatocyte. Newly developed meiotic proteins antibodies (anti-SCP3, anti-synaptonemal complex proteins 3, anti-MLH1, anti-Mut-L Homolog 1, anti-CREST, chromosome centromere antibody) were used to identify synaptonemal complex (anti-SCP3), recombination sites (anti-MLH1) and centromere (anti-CREST), respectively. Staging of spermatocyte was determined according to SCP3 formation progression. Qualitative data were compared by a Chi-square test, and ANOVA was used to analyze quantitative data.

RESULTSRespectively, 2346 and 2932 spermatocytes were categorized in the controls and azoospermic patients. The proportions of zygotene cells in both OA group and NOA group were significantly higher than that of the control group. Investigation of 1967 pachytene cells from the controls and 354 pachytene cells from azoospermic patients indicated that the mean MLH1 foci per pachytene cell of NOA group was statistically lower than that of the controls. Compared with the controls, incomplete synaptonemal complexes cells (containing gap and/or split) were significantly increased in the NOA group.

CONCLUSIONDelayed meiosis prophase is relatively common in azoospermic patients, and changes in quantity and distribution of recombination foci may be the cause for spermatogenesis arrest in Han Chinese population.

Adult ; Asian Continental Ancestry Group ; Azoospermia ; genetics ; metabolism ; pathology ; Humans ; Male ; Meiosis ; genetics ; Middle Aged ; Recombination, Genetic ; Spermatocytes ; metabolism ; Synaptonemal Complex ; genetics ; Young Adult