Regions of differential cell elongation and mitosis, and root meristem morphology in different tissues of geotropically stimulated maize root apices
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Shen-Miller, J.↗
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Results for “MITOSIS”
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Microtubule configurations during fertilization, mitosis, and early development in the mouse and the requirement for egg microtubule-mediated motility during mammalian fertilization
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Schatten, G.↗
Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA)
Highlights: •NuMA is modified by SUMO-1 in a cell cycle-dependent manner. •NuMA lysine 1766 is the primary target site for SUMOylation. •SUMOylation-deficient NuMA induces multiple spindle poles during mitosis. •SUMOylated NuMA induces microtubule bundling. -- Abstract: Covalent conjugation of proteins with small ubiquitin-like modifier 1 (SUMO-1) plays a critical role in a variety of cellular functions including cell cycle control, replication, and transcriptional regulation. Nuclear mitotic apparatus protein (NuMA) localizes to spindle poles during mitosis, and is an essential component in the formation and maintenance of mitotic spindle poles. Here we show that NuMA is a target for covalent conjugation to SUMO-1. We find that the lysine 1766 residue is the primary NuMA acceptor site for SUMO-1 conjugation. Interestingly, SUMO modification of endogenous NuMA occurs at the entry into mitosis and this modification is reversed after exiting from mitosis. Knockdown of Ubc9 or forced expression of SENP1 results in impairment of the localization of NuMA to mitotic spindle poles during mitosis. The SUMOylation-deficient NuMA mutant is defective in microtubule bundling, and multiple spindles are induced during mitosis. The mitosis-dependent dynamic SUMO-1 modification of NuMA might contribute to NuMA-mediated formation and maintenance of mitotic spindle poles during mitosis.
60 APPLIED LIFE SCIENCES↗
Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin
During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression. -- Highlights: Black-Right-Pointing-Pointer Global genome repair of (6-4) photoproducts is fully active in mitotic cells. Black-Right-Pointing-Pointer DNA in condensed mitotic chromatin does not seem inaccessible or inert. Black-Right-Pointing-Pointer Mitotic transcriptional repression may impair transcription-coupled repair.
60 APPLIED LIFE SCIENCES↗
γ-Taxilin temporally regulates centrosome disjunction in a Nek2A-dependent manner
Highlights: • γ-Taxilin co-localizes with Nek2A at the centrosome during interphase. • γ-Taxilin interacts with Nek2A in yeast two-hybrid and pull-down assays. • γ-Taxilin protein expression levels decrease at the onset of mitosis. • γ-Taxilin depletion induces immature splitting of centrosomes. • The immature splitting of centrosomes induced by γ-taxilin depletion depends on Nek2A. Never in mitosis A-related kinase 2A (Nek2A), a centrosomal serine/threonine kinase, is involved in mitotic progression by regulating the centrosome cycle. Particularly, Nek2A is necessary for dissolution of the intercentriole linkage between the duplicated centrosomes prior to mitosis. Nek2A activity roughly parallels its cell cycle-dependent expression levels, but the precise mechanism regulating its activity remains unclear. In this study, we found that γ-taxilin co-localized with Nek2A at the centrosome during interphase and interacted with Nek2A in yeast two-hybrid and pull-down assays and that γ-taxilin regulated centrosome disjunction in a Nek2A-dependent manner. γ-Taxilin depletion increased the number of cells with striking splitting of centrosomes. The precocious splitting of centrosomes induced by γ-taxilin depletion was attenuated by Nek2A depletion, suggesting that γ-taxilin depletion induces the Nek2A-mediated dissolution of the intercentriole linkage between the duplicated centrosomes nevertheless mitosis does not yet begin. Taken together with the result that γ-taxilin protein expression levels were decreased at the onset of mitosis, we propose that γ-taxilin participates in Nek2A-mediated centrosome disjunction as a negative regulator through its interaction with Nek2A.
60 APPLIED LIFE SCIENCES↗
Early and Late Chromosome Damages in Human Lymphocytes Induced by Gamma Rays and Fe Ions
Chromosomal translocations and inversions are considered stable, and cells containing these types of chromosome aberrations can survive multiple cell divisions. An efficient method to detect an inversion is multi-color banding fluorescent in situ hybridization (mBAND) which allows identification of both inter- and intrachromosome aberrations simultaneously. Post irradiation, chromosome aberrations may also arise after multiple cell divisions as a result of genomic instability. To investigate the stable or late-arising chromosome aberrations induced after radiation exposure, we exposed human lymphocytes to gamma rays and Fe ions ex vivo, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis and at several time intervals during the culture period post irradiation. With gamma irradiation, about half of the damages observed at first mitosis remained after 7 day- and 14 day- culture, suggesting the transmissibility of damages to the surviving progeny. Detailed analysis of chromosome break ends participating in exchanges revealed a greater fraction of break ends involved in intrachromosome aberrations in the 7- and 14-day samples in comparison to the fraction at first mitosis. In particular, simple inversions were found at 7 and 14 days, but not at the first mitosis, suggesting that some of the aberrations might be formed days post irradiation. In contrast, at the doses that produced similar frequencies of gamma-induced chromosome aberrations as observed at first mitosis, a significantly lower yield of aberrations remained at the same population doublings after Fe ion exposure. At these equitoxic doses, more complex type aberrations were observed for Fe ions, indicating that Fe ion-induced initial chromosome damages are more severe and may lead to cell death. Comparison between low and high doses of Fe ion irradiation in the induction of late damages will also be discussed.
Sunagawa, Mayumi↗
mBAND Analysis of Late Chromosome Aberrations in Human Lymphocytes Induced by Gamma Rays and Fe Ions
Chromosomal translocations and inversions are considered stable, and cells containing these types of chromosome aberrations can survive multiple cell divisions. An efficient method to detect an inversion is multi-color banding fluorescent in situ hybridization (mBAND) which allows identification of both inter- and intrachromosome aberrations simultaneously. Post irradiation, chromosome aberrations may also arise after multiple cell divisions as a result of genomic instability. To investigate the stable or late-arising chromosome aberrations induced after radiation exposure, we exposed human lymphocytes to gamma rays and Fe ions ex vivo, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis and at several time intervals during the culture period post irradiation. With gamma irradiation, about half of the damages observed at first mitosis remained after 7 day- and 14 day- culture, suggesting the transmissibility of damages to the surviving progeny. Detailed analysis of chromosome break ends participating in exchanges revealed a greater fraction of break ends involved in intrachromosome aberrations in the 7- and 14-day samples in comparison to the fraction at first mitosis. In particular, simple inversions were found at 7 and 14 days, but not at the first mitosis, suggesting that some of the aberrations might be formed days post irradiation. In contrast, at the doses that produced similar frequencies of gamma-induced chromosome aberrations as observed at first mitosis, a significantly lower yield of aberrations remained at the same population doublings after Fe ion exposure. At these equitoxic doses, more complex type aberrations were observed for Fe ions, indicating that Fe ion-induced initial chromosome damages are more severe and may lead to cell death. Comparison between low and high doses of Fe ion irradiation in the induction of late damages will also be discussed.
Sunagawa, Mayumi↗
Feasibility of using computed tomography texture analysis parameters as imaging biomarkers for predicting risk grade of gastrointestinal stromal tumors: comparison with visual inspection
Purpose: To evaluate the feasibility of using computed tomography texture analysis (CTTA) parameters for predicting malignant risk grade and mitosis index of gastrointestinal stromal tumors (GISTs), compared with visual inspection. Method and materials: CTTA was performed on portal phase CT images of 145 surgically confirmed GISTs (mean size: 42.9 ± 37.5 mm), using TexRAD software. Mean, standard deviation, entropy, mean of positive pixels (MPP), skewness, and kurtosis of CTTA parameters, on spatial scaling factor (SSF), 2–6 were compared by risk grade, mitosis rate, and the presence or absence of necrosis on visual inspection. CTTA parameters were correlated with risk grade. Diagnostic performance was evaluated with receiver operating characteristic curve analysis. Enhancement pattern, necrosis, heterogeneity, calcification, growth pattern, and mucosal ulceration were subjectively evaluated by two observers. Results: Three to four parameters at different scales were significantly different according to the risk grade, mitosis rate, and the presence or absence of necrosis (p < 0.041). MPP at fine or medium scale (r = − 0.547 to − 393) and kurtosis at coarse scale (r = 0.424–0.454) correlated significantly with risk grade (p < 0.001). HG-GIST was best differentiated from LG-GIST by MPP at SSF 2 (AUC, 0.782), and kurtosis at SSF 4 (AUC, 0.779) (all p < 0.001). CT features predictive of HG-GIST were density lower than or equal to that of the erector spinae muscles on enhanced images (OR 2.1; p = 0.037; AUC, 0.59), necrosis (OR, 6.1; p < 0.001; AUC, 0.70), heterogeneity (OR, 4.3; p < 0.001; AUC, 0.67), and mucosal ulceration (OR, 3.3; p = 0.002; AUC, 0.62). Conclusion: Using TexRAD, MPP and kurtosis are feasible in predicting risk grade and mitosis index of GISTs. CTTA demonstrated meaningful accuracy in preoperative risk stratification of GISTs.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Mitotic phosphorylation of VCIP135 blocks p97ATPase-mediated Golgi membrane fusion
Highlights: •VCIP135 is mitotically phosphorylated on Threonine-760 and Serine-767 by Cdc2. •Phosphorylated VCIP135 does not bind to p97ATPase. •The phosphorylation of VCIP135 inhibits p97ATPase-mediated Golgi membrane fusion. -- Abstract: In mammals, the Golgi apparatus is disassembled early mitosis and reassembled at the end of mitosis. For Golgi disassembly, membrane fusion needs to be blocked. Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. We previously reported that p47 phosphorylation on Serine-140 and p37 phosphorylation on Serine-56 and Threonine-59 result in mitotic inhibition of the p97/p47 and the p97/p37 pathways, respectively [11,14]. In this study, we show another mechanism of mitotic inhibition of p97-mediated Golgi membrane fusion. We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97. An in vitro Golgi reassembly assay revealed that VCIP135(T760E, S767E), which mimics mitotic phosphorylation, caused no cisternal regrowth. Our results indicate that the phosphorylation of VCIP135 on Threonine-760 and Serine-767 inhibits p97-mediated Golgi membrane fusion at mitosis.
60 APPLIED LIFE SCIENCES↗
The moyamoya disease susceptibility variant RNF213 R4810K (rs112735431) induces genomic instability by mitotic abnormality
Highlights: •Overexpression of RNF213 R4810K inhibited cell proliferation. •Overexpression of RNF213 R4810K had the time of mitosis 4-fold and mitotic failure. •R4810K formed a complex with MAD2 more readily than wild-type. •iPSECs from the MMD patients had elevated mitotic failure compared from the control. •RNF213 R4810K induced mitotic abnormality and increased risk of aneuploidy. -- Abstract: Moyamoya disease (MMD) is a cerebrovascular disease characterized by occlusive lesions in the Circle of Willis. The RNF213 R4810K polymorphism increases susceptibility to MMD. In the present study, we characterized phenotypes caused by overexpression of RNF213 wild type and R4810K variant in the cell cycle to investigate the mechanism of proliferation inhibition. Overexpression of RNF213 R4810K in HeLa cells inhibited cell proliferation and extended the time of mitosis 4-fold. Ablation of spindle checkpoint by depletion of mitotic arrest deficiency 2 (MAD2) did not shorten the time of mitosis. Mitotic morphology in HeLa cells revealed that MAD2 colocalized with RNF213 R4810K. Immunoprecipitation revealed an RNF213/MAD2 complex: R4810K formed a complex with MAD2 more readily than RNF213 wild-type. Desynchronized localization of MAD2 was observed more frequently during mitosis in fibroblasts from patients (n = 3, 61.0 ± 8.2%) compared with wild-type subjects (n = 6, 13.1 ± 7.7%; p < 0.01). Aneuploidy was observed more frequently in fibroblasts (p < 0.01) and induced pluripotent stem cells (iPSCs) (p < 0.03) from patients than from wild-type subjects. Vascular endothelial cells differentiated from iPSCs (iPSECs) of patients and an unaffected carrier had a longer time from prometaphase to metaphase than those from controls (p < 0.05). iPSECs from the patients and unaffected carrier had significantly increased mitotic failure rates compared with controls (p < 0.05). Thus, RNF213 R4810K induced mitotic abnormalities and increased risk of genomic instability.
60 APPLIED LIFE SCIENCES↗
Aurora A regulates the architecture of the Golgi apparatus
Highlights: • Knockdown or inhibition of Aurora A resulted in Golgi dispersal during interphase. • Overexpression of Aurora A led to tightly packed Golgi apparatus during interphase. • Inhibition of Aurora A induced Golgi dispersal after mitosis. • Knockdown or inhibition of Aurora A also led to disruption in integrity of centrosome and Golgi apparatus during interphase. The Golgi apparatus plays roles in cell polarity, directional cell migration, and bipolar spindle assembly, as well as the secretary pathway. In addition, recent studies have suggested the Golgi-dependent control of mitotic entry. We studied the role of the centrosomal kinase Aurora A in maintaining the Golgi apparatus. Knockdown of Aurora A resulted in Golgi dispersal during interphase. Golgi dispersal was also induced by a selective Aurora A inhibitor, MLN8237. Conversely, overexpression of Aurora A led to tightly packed Golgi apparatus during interphase. Knockdown or inhibition of Aurora A had little or no effect on Golgi vesiculation during mitosis. By synchronizing cell division, we studied whether mitosis was required to induce Golgi dispersal during interphase. Aurora A inhibition induced aberrant mitotic spindle and Golgi dispersal only after mitosis. However, the cells treated with the inhibitor MLN8237 at earlier cell cycle stages (wherein the cells remained undivided) had a normal Golgi architecture. Knockdown or inhibition of Aurora A also led to aberrant integrity of centrosome and Golgi apparatus during interphase. These results suggest that Aurora A activity is involved in the maintenance of Golgi architecture and the relationship between the Golgi apparatus and centrosome.
60 APPLIED LIFE SCIENCES↗
Cellular localization of ATBF1 protein and its functional implication in breast epithelial cells
ATBF1, a large transcription factor, was normally localized in nuclei, and its mislocalization to cytoplasm was reported in multiple cancers. However, localization of ATBF1 in breast epithelial cells and its potential functions were unknown. Here, we investigated ATBF1 localization via immunofluorescence staining in different kinds of breast epithelial cells. In MCF10A cells and normal mice mammary gland tissues, ATBF1 was mainly localized in nuclei. Knockdown of ATBF1 expression in MCF10A cells by siRNA promoted cell proliferation. Moreover, ATBF1 was co-localized with chromosome during mitosis, indicating its potential function in mitosis. In an estrogen receptor (ER)-positive breast cancer cell line (MCF7), estrogen induced ATBF1 translocation from cytoplasm to nuclei in an ER dependent pathway. In ER-negative cells (Hs578T and MDA-MB-231), ATBF1 was co-localized with GM130 in cytoplasm, indicating ATBF1 localization was associated with protein modification in golgi body. The results were beneficial for intensive investigation of ATBF1's function with different cellular localization in breast cancer. - Highlights: • Cellular localization of ATBF1 is correlated with its function in breast cancer. • Nuclear ATBF1 was co-localized with chromosome during mitosis normally. • Estrogen induced translocation of cytoplasmic ATBF1 to nuclei in MCF7. • Translocation of ATBF1 in ER{sup +} breast cancer cells was ER dependent. • Cytoplasmic ATBF1 was co-localized with golgi body in ER{sup −} breast cancer cells.
60 APPLIED LIFE SCIENCES↗
Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice
Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5 mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis–vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43–57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5 mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5 mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5 mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation. - Highlights: • Methamidophos alters sperm cell function at different stages of spermatogenesis. • Testicular stages of spermatogenesis are more sensitive to methamidophos toxicity. • Methamidophos causes sperm DNA damage at mitosis, meiosis and epididymal maturation. • Sperm cell damage by methamidophos exposure may be related to protein phosphorylation.
60 APPLIED LIFE SCIENCES↗
Light differentially regulates cell division and the mRNA abundance of pea nucleolin during de-etiolation
The abundance of plant nucleolin mRNA is regulated during de-etiolation by phytochrome. A close correlation between the mRNA abundance of nucleolin and mitosis has also been previously reported. These results raised the question of whether the effects of light on nucleolin mRNA expression were a consequence of light effects on mitosis. To test this we compared the kinetics of light-mediated increases in cell proliferation with that of light-mediated changes in the abundance of nucleolin mRNA using plumules of dark-grown pea (Pisum sativum) seedlings. These experiments show that S-phase increases 9 h after a red light pulse, followed by M-phase increases in the plumule leaves at 12 h post-irradiation, a time course consistent with separately measured kinetics of red light-induced increases in the expression of cell cycle-regulated genes. These increases in cell cycle-regulated genes are photoreversible, implying that the light-induced increases in cell proliferation are, like nucleolin mRNA expression, regulated via phytochrome. Red light stimulates increases in the mRNA for nucleolin at 6 h post-irradiation, prior to any cell proliferation changes and concurrent with the reported timing of phytochrome-mediated increases of rRNA abundance. After a green light pulse, nucleolin mRNA levels increase without increasing S-phase or M-phase. Studies in animals and yeast indicate that nucleolin plays a significant role in ribosome biosynthesis. Consistent with this function, pea nucleolin can rescue nucleolin deletion mutants of yeast that are defective in rRNA synthesis. Our data show that during de-etiolation, the increased expression of nucleolin mRNA is more directly regulated by light than by mitosis.
NASA Program Fundamental Space Biology↗
Comparison of F ratios generated from interphase and metaphase chromosome damage induced by high doses of low- and high-LET radiation
Although biophysical models predict a difference in the ratio of interchromosomal to intrachromosomal interarm exchanges (F ratio) for low- and high-LET radiations, few experimental data support this prediction. However, the F ratios in experiments to date have been generated using data on chromosome aberrations in samples collected at the first postirradiation mitosis, which may not be indicative of the aberrations formed in interphase after exposure to high-LET radiations. In the present study, we exposed human lymphocytes in vitro to 2 and 5 Gy of gamma rays and 3 Gy of 1 GeV/nucleon iron ions (LET = 140 keV/micrometer), stimulated the cells to grow with phytohemagglutinin (PHA), and collected the condensed chromosomes after 48 h of incubation using both chemically induced premature chromosome condensation (PCC) and the conventional metaphase techniques. The PCC technique used here condenses chromosomes mostly in the G(2) phase of the cell cycle. The F ratio was calculated using data on asymmetrical chromosome aberrations in both the PCC and metaphase samples. It was found that the F ratios were similar for the samples irradiated with low- and high-LET radiation and collected at metaphase. However, for irradiated samples assayed by PCC, the F ratio was found to be 8.2 +/- 2.0 for 5 Gy gamma rays and 5.2 +/- 0.9 for 3 Gy iron ions. The distribution of the aberrations indicated that, in the PCC samples irradiated with iron ions, most of the centric rings occurred in spreads containing five or more asymmetrical aberrations. These heavily damaged cells, which were either less likely to reach mitosis or may reach mitosis at a later time, were responsible for the difference in the F ratios generated from interphase and metaphase analysis after exposure to iron ions.
NASA Discipline Radiation Health↗
Centrosome structure and function is altered by chloral hydrate and diazepam during the first reproductive cell cycles in sea urchin eggs
This paper explores the mode of action of the tranquillizers chloral hydrate and diazepam during fertilization and mitosis of the first reproductive cell cycles in sea urchin eggs. Most striking effects of these drugs are the alteration of centrosomal material and the abnormal microtubule configurations during exposure and after recovery from the drugs. This finding is utilized to study the mechanisms of centrosome compaction and decompaction and the dynamic configurational changes of centrosomal material and its interactions with microtubules. When 0.1% chloral hydrate or 350-750 microM diazepam is applied at specific phases during the first cell cycle of sea urchin eggs, expanded centrosomal material compacts at distinct regions and super-compacts into dense spheres while microtubules disassemble. When eggs are treated before pronuclear fusion, centrosomal material aggregates around each of the two pronuclei while microtubules disappear. Upon recovery, atypical asters oftentimes with multiple foci are formed from centrosomal material surrounding the pronuclei which indicates that the drugs have affected centrosomal material and prevent it from functioning normally. Electron microscopy and immunofluorescence studies with antibodies that routinely stain centrosomes in sea urchin eggs (4D2; and Ah-6) depict centrosomal material that is altered when compared to control cells. This centrosomal material is not able to reform normal microtubule patterns upon recovery but will form multiple asters around the two pronuclei. When cells are treated with 0.1% chloral hydrate or 350-750 microM diazepam during mitosis, the bipolar centrosomal material becomes compacted and aggregates into multiple dense spheres while spindle and polar microtubules disassemble. With increased incubation time, the smaller dense centrosome particles aggregate into bigger and fewer spheres. Upon recovery, unusual irregular microtubule configurations are formed from centrosomes that have lost their ability to reform normal mitotic figures. These results indicate that chloral hydrate and diazepam affect centrosome structure which results in the inability to reform normal microtubule formations and causes abnormal fertilization and mitosis.
Non-NASA Center↗
mBAND Analysis of Early and Late Damages in the Chromosome of Human Lymphocytes after Exposures to Gamma Rays and Fe Ions
Stable type chromosome aberrations that survive multiple generations of cell division include translocation and inversions. An efficient method to detect an inversion is multi-color banding fluorescent in situ hybridization (mBAND) which allows identification of both inter- and intrachromosome aberrations simultaneously. Post irradiation, chromosome aberrations may also arise after multiple cell divisions as a result of genomic instability. To investigate the stable or late-arising chromosome aberrations induced after radiation exposure, we exposed human lymphocytes to gamma rays and Fe ions ex vivo, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis and at several time intervals during the culture period post irradiation. With gamma irradiation, about half of the damages observed at first mitosis remained after 7 day- and 14 day- culture, suggesting the transmissibility of damages to the surviving progeny. At the doses that produced similar frequencies of gamma-induced chromosome aberrations as observed at first mitosis, a significantly lower yield of aberrations remained at the same population doublings after Fe ion exposure. At these equitoxic doses, more complex type aberrations were observed for Fe ions, indicating that Fe ion-induced initial chromosome damages are more severe and may lead to cell death. Detailed analysis of breaks participating in total chromosome exchanges within the first cell cycle post irradiation revealed a common hotspot located in the 3p21 region, which is a known fragile site corresponding to the band 6 in the mBand analysis. The breakpoint distribution in chromosomes collected at 7 days, but not at 14 days, post irradiation appeared similar to the distribution in cells collected within the first cell cycle post irradiation. The breakpoint distribution for human lymphocytes after radiation exposure was different from the previously published distribution for human mammary epithelial cells, indicating that interphase chromatin folding structures play a role in the distribution of radiation-induced breaks.
Sunagawa, Mayumi↗
Bistability analysis in mathematical model of M-phase control in Xenopus oocyte extracts
To gain more insight into the molecular mechanism that regulates eukaryotic cell cycle, we propose a modification to an existing Mathematical model of mitosis-promoting factor control in Xenopus oocyte extract. To achieve this, we redirect how cell exits from mitosis using ubiquitin ligase enzyme APCP:Cdc20 which is acting as a modifier in cyclin degradation. We present a modified wiring map using combination of mass action kinetics and Michaelis–Menten kinetics to represent the biochemical processes. This results in a system of non-linear ordinary differential equations. The equilibria of the system were analyzed analytically. Using MPF as a bifurcation parameter, we analytically derived conditions under which bistability can occur in the MPF activation module. We find that for bistability to occur, it is necessary that the rate of phosphorylation of Wee1 must be greater than the rate of its dephosphorylation and that the concentration of MPF must lie in certain range of parameter values. Numerical simulations conducted show that the time taken to exit the cell cycle is shorter than those published in some reports and the sensitivity analysis results suggest that the rate of synthesis of cyclin is the most sensitive parameter in the dynamics of cell cycle. Through numerical experiments, we found new parameter sets that will give rise to bistability in the MPF activation module.
97 MATHEMATICS AND COMPUTING↗