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1.
Shashank Hambarde Chi-Lin Tsai Raj K. Pandita Albino Bacolla Anirban Maitra Vijay Charaka Clayton R. Hunt Rakesh Kumar Oliver Limbo Remy Le Meur Walter J. Chazin Susan E. Tsutakawa Paul Russell Katharina Schlacher Tej K. Pandita John A. Tainer 《Molecular cell》2021,81(14):2989-3006.e9
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Mitosis is the key event of the cell cycle during which the sister chromatids are segregated onto two daughter cells. It is well established that abrogation of the normal mitotic progression is a highly efficient concept for anti‐cancer treatment. In fact, various drugs that target microtubules and thus interfere with the function of the mitotic spindle are in clinical use for the treatment of various human malignancies for many years. However, since microtubule inhibitors not only target proliferating cells severe side effects limit their use. Therefore, the identification of novel mitotic drug targets other than microtubules have gained recently much attention. This review will summarize the latest developments on the identification and clinical evaluation of novel mitotic drug targets and will introduce novel concepts for chemotherapy that are based on recent progress in our understanding how mitotic progression is regulated and how anti‐mitotic drugs induce tumor cell death. J. Cell. Biochem. 111: 258–265, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
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S. E. Ashmore A. S. Shapcott 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1989,78(2):249-259
Summary Investigations have been carried out on karyotype change in both callus and suspension cell cultures of Haplopappus gracilis (2n=4). It has been found that polyploidization arises directly in culture to give up to six times the normal diploid chromosome number in some cultures. In polyploid cultures, both chromosome loss and chromosome rearrangements occur to give rise to aneuploid karyotypes displaying chromosomes which differ in morphology from the diploid set. Whole or partial chromosome loss has been observed in the form of lagging chromosomes and chromosome bridges at anaphase, and micronuclei, ring chromosomes and chromosome fragments at other stages in mitosis. C-banded preparations have confirmed the occurrence of chromosomal rearrangements. Comparative investigations suggest that (i) more polyploidy occurs in callus cultures than in suspension cell cultures, and (ii) the presence of cytokinin (kinetin) in the culture medium may reduce the extent of karyotype change. 相似文献
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T. Endo T. Komiya M. Mino K. Nakanishi S. Fujita Y. Yamada 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1988,76(5):641-646
Summary The genetic instability of an intertribal hybrid cell line, Duboisia hopwoodii + Nicotiana tabacum, obtained by mechanical isolation of a single hybrid cell was studied. Ten subclones of calli derived from this hybrid cell line were cultured for 3 years, and their genetic makeup clarified as to nuclear DNA content, chromosome constitution, and peroxidase isozymes. Nuclear DNA content differed in each subclone. In most subclones, mean DNA content was lower than the mean DNA content in the original hybrid cell line determined 1 year after fusion. This decrease in DNA content is partly attributable to the elimination of tobacco chromosomes that occurred in all subclones. The extent to which tobacco chromosomes were eliminated varied among the subclones — evidence that chromosome elimination occurred slowly. Peroxidase isozyme analysis indicated the loss of a tobacco-specific isozyme, thus confirming results obtained by chromosome analysis. Shoots regenerated from two hybrid subclones after 2 years were also heterogeneous in morphology and nuclear DNA content. 相似文献
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Valeria Cavaliere Franco Graziani Silvia Andone Andrea Manzi Carla Malva 《Molecular & general genetics : MGG》1991,230(3):433-441
Summary The abnormal oocyte phenotype is characterized by instability, as shown by the loss and reappearance of the abo maternal effect under specific genetic conditions. Our previous finding that a correlation exists between the abo phenotype and the presence of a blood transposon in region 32E, led us to perform an extensive genetic and molecular analysis of the most significant aspects of the abo phenotype in different genetic backgrounds. The results of these experiments can be summarized as follows: Complete reversion occurs only when the blood transposon is lost, thus definitively demonstrating that the insertion of the blood transposon in region 32E is the molecular event that causes the pleiotropic abo phenotype. Partial reversion can also occur without loss of the transposon, indicating that different molecular pathways may be involved in the loss of the abo phenotype. Reappearance of the full abo phenotype can occur only in heterozygous lines constructed from partially revertant abo homozygous lines that have not lost the blood transposon. 相似文献
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Claire Domon Jean-Luc Evrard Datta T.N. Pillay André Steinmetz 《Molecular & general genetics : MGG》1991,229(2):238-244
Summary Metabolism of sulfonylurea herbicides by Streptomyces griseolus ATCC 11796 is carried out via two cytochromes P-450, P-450SU1 and P-450SU2. Mutants of S. griseolus, selected by their reduced ability to metabolize a fluorescent sulfonylurea, do not synthesize cytochrome P-450SU1 when grown in the presence of sulfonylureas. Genetic evidence indicated that this phenotype was the result of a deletion of > 15 kb of DNA, including the structural genes for cytochrome P-450SU1 and an associated ferredoxin Fd-1 (suaC and suaB, respectively). In the absence of this monooxygenase system, the mutants described here respond to the presence of sulfonylureas or phenobarbital in the growth medium with the expression of only the suhC,B gene products (cytochrome P-450SU2 and Fd-2), previously observed only as minor components in wild-type cells treated with sulfonylurea. These strains have enabled an analysis of sulfonylurea metabolism mediated by cytochrome P-450SU2 in the absence of P-450SU1, yielding an in vivo delineation of the roles of the two different cytochrome P-450 systems in herbicide metabolism by S. griseolus. 相似文献
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In extracts of flax seedlings 4 days after imbibition, isocitrate lyase activity is unstable in comparison to that in extracts from 2.5-day seedlings or to malate syntheses analysed at several stages of development. This instability in extracts of 4-day seedlings is especially pronounced when a large number of seedlings is homogenized per unit volume of Tris-Mg2+-EDTA-dithioerythritol buffer. However, isocitrate lyase can be stabilized when the resultant homogenate is diluted soon after seedling breakage. The pronounced instability in more concentrated extracts is not due to inadequate buffering by the homogenization medium, nor can it be due to polyphenols because added polyvinylpyrrolidone has no effect. Mixing of a heated supernatant from concentrated extract with dilute unheated extract yields the units of stable isocitrate lyase expected in the dilute extract, ruling out stoichiometric inactivation by a heat-stable component. The pronounced instability is attributed to the action of proteinases. A theoretical model assuming a decay process that is first order in isocitrate lyase and first-order in one or more proteinases is in reasonable agreement with the results. Malate synthase and NADP+-isocitrate dehydrogenase are much more stable in concentrated extracts prepared from 4-day flax seedlings. Isocitrate lyase is stable in concentrated extracts of 5-day watermelon seedlings, which is a developmental stage analogous to that for 4-day flax seedlings. 相似文献
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V Meininger S Binet E Chaineau A Fellous 《Biology of the cell / under the auspices of the European Cell Biology Organization》1990,68(1):21-29
The response of microtubules to treatment with vinca alkaloids was investigated in vivo and in situ in the embryonic nervous system of mice. For this purpose we used rotatory cultures of post-implanted embryos in a serum medium containing the alkaloid combined with immunofluorescence using a tubulin-specific polyclonal antibody on high molecular weight polyethylene glycol embedded semithin sections. In mitotic cells, kinetochore microtubules were seen to be more resistant to the action of vinca alkaloids than interpolar microtubules. Increasing drug concentrations induced an increasing rate of mitosis together with an increasing rate of disassembly of the cytoplasmic microtubule complex, suggesting a probable relation between these events. In bipolar neuroepithelial cells at interphase, a small pool of microtubules was resistant to the vinca alkaloids. These microtubules were located near the centriolar apparatus associated with the primary cilium; they were short, curly and bent. Disruption of the cytoplasmic microtubule complex did not alter the shape of the bipolar neuroepithelial cells. In the axonal profiles, a drug-stable pool of microtubules were not disrupted by the alkaloids and were also short. They seem to act as microtubule organizing centres. These observations suggest vinca alkaloids seem to act in vivo much more by inducing, at a given concentration, the disruption of a particular group of microtubules without altering the others. The fact that these drugs affect the number, but not the length, of the microtubules raises the hypothesis that these drugs act on microtubules by a mechanism similar to that described as "dynamic instability". 相似文献