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A time and a place
headlines fertilization chamber), and male spe-9 mutants can successfully copulate with and ejaculate into wild-type hermaphrodites. However, despite documented intimate interaction between gametes, spe-9 mutant sperm are not recognized by wild-type eggs. Cloning revealed that the spe-9 gene contains a signal sequence and 10 epidermal growth factor (EGF)-like repeats, a motif found in many proteins involved in extracellular functions. The structure of spe-9 is similar to the Notch/ LIN-12/GLP-1 class of ligands, suggesting that the protein encoded by spe-9 is on the sperm surface and functions as a ligand for an egg receptor. The finding that two spe-9 mutant alleles contain point mutations in one of the EGF-like repeats supports this hypothesis. However, whether the protein encoded by spe-9 is expressed by spermatozoa, is localized to the sperm membrane or even interacts with the egg have yet to be determined. While more-conclusive experiments are required to evaluate spe-9 function, this system provides a much needed genetic component to fertilization research.
A time and a place POMBO, A. et al. (1998) Regional and temporal specialization in the nucleus: a transcriptionally-active nuclear domain rich in PTF, Oct1 and PIKA antigens associates with specific chromosomes early in the cell cycle EMBO J. 17, 1768–1778 In the past few years, numerous subcompartments have been identified within the mammalian cell nucleus. The function of these nuclear compartments has been enigmatic. One key question to address their function is whether their position within the nucleus is random or is related to functions they might exert. A strong argument for nonrandom localization of nuclear bodies comes now from the study of transcription-factor distribution. The transcription factors PTF and Oct1 are involved in the activation of genes encoding snRNAs and are activators of RNA polymerases II and III. The two proteins are distributed in local concentrations throughout the nucleoplasm but are also found in prominent nuclear domains in late G1 phase and S phase. The domain is typically near the nucleolus, contains RNA polymerase II and active sites of transcription and was therefore named OPT (for Oct1/PTF-transcription) domain. OPT domains do not contain components of the splicing machinery, which is interesting in the light of the fact that the Oct1/PTF target genes are known not to contain introns. Most importantly, the OPT domain appears preferentially associated with chromosomes 6 and 7, and specifically a 30-Mb region of chromosome 6 was mapped to associate frequently with the domain. These observations suggest that the position of the OPT domain with respect to chromosomes is not random but is rather the result of a transcriptional hot-spot of genes activated by Oct1 and PTF. Together with the facts that the nucleolus forms around transcriptionally highly active ribosomal genes and that another nuclear body, the coiled body, has been reported to be associated preferentially with several snRNA genes, it can now be speculated that nuclear bodies might represent sites of high levels of trends in CELL BIOLOGY (Vol. 8) July 1998
transcriptional activity of particular genes. This is an intriguing and testable concept that once again confirms the emerging view that nuclear structure is crucial for the orchestration of nuclear functions.
Nuclear waste disposal SHIMIZU, N., ITOH, N., UTIYAMA, H. and WAHL, G. (1998) Selective entrapment of extrachromosomally amplified DNA by nuclear budding and micronucleation during S phase J. Cell Biol. 140, 1307–1320 Certain cancer cells accumulate aberrant chromosomal structures, such as circular, autonomously replicating double-minute chromosomes (DMs). The acentric DMs arise at high frequency in cells that have been treated with cytostatic drugs and thus are thought to be responsible for drug-resistant tumours. Wahl and collaborators now present a morphological characterization of a process termed micronucleation that functions in the removal of such aberrant structures from the nucleus. Interestingly, in synchronized tissue-culture cells, the DMs are included into small, membraneenclosed structures that arise from the nuclear envelope during S phase, when the nuclear envelope is intact. This mechanism is a viable alternative to the previously observed nuclear envelope condensation during postmitotic nuclear reassembly that also can result in micronucleus formation. The S-phase-specific micronucleation process seems to be enhanced by treating cells with replication inhibitors, offering a strategy for how to extrude DMs from tumour cells and thus increase their sensitivity to cytostatic drugs. The fact that these micronuclei only form in the presence of DMs predicts that the cell must employ a mechanism to recognize acentric DNA and initiate a series of events that ultimately lead to inclusion of the deviant DNA into a nuclear-envelope-enclosed vesicle. The micronuclei must then be targeted for either extrusion from the cell or internal degradation. Further studies aimed at understanding the signals that induce micronucleation and the molecular mechanism of this important cellular event should unravel an interesting signal-transduction pathway.
Biofilm, starring… DAVIES, D. G., PARSEK, M. R., PEARSON, J. P., IGLEWSKI, B. H., COSTERTON, J. W. and GREENBERG, E. P. (1998) The involvement of cell-to-cell signals in the development of a bacterial biofilm Science 280, 295–298 Most bacteria develop a mechanism for adhering to solid surfaces to establish complex communities known as biofilms. These consist of differentiated mushroom- and
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A time and a place POMBO, A. et al. (1998) Regional and temporal specialization in the nucleus: a transcriptionally-active nuclear domain rich in PTF, Oct1 and PIKA antigens associates with specific chromosomes early in the cell cycle EMBO J. 17, 1768–1778 In the past few years, numerous subcompartments have been identified within the mammalian cell nucleus. The function of these nuclear compartments has been enigmatic. One key question to address their function is whether their position within the nucleus is random or is related to functions they might exert. A strong argument for nonrandom localization of nuclear bodies comes now from the study of transcription-factor distribution. The transcription factors PTF and Oct1 are involved in the activation of genes encoding snRNAs and are activators of RNA polymerases II and III. The two proteins are distributed in local concentrations throughout the nucleoplasm but are also found in prominent nuclear domains in late G1 phase and S phase. The domain is typically near the nucleolus, contains RNA polymerase II and active sites of transcription and was therefore named OPT (for Oct1/PTF-transcription) domain. OPT domains do not contain components of the splicing machinery, which is interesting in the light of the fact that the Oct1/PTF target genes are known not to contain introns. Most importantly, the OPT domain appears preferentially associated with chromosomes 6 and 7, and specifically a 30-Mb region of chromosome 6 was mapped to associate frequently with the domain. These observations suggest that the position of the OPT domain with respect to chromosomes is not random but is rather the result of a transcriptional hot-spot of genes activated by Oct1 and PTF. Together with the facts that the nucleolus forms around transcriptionally highly active ribosomal genes and that another nuclear body, the coiled body, has been reported to be associated preferentially with several snRNA genes, it can now be speculated that nuclear bodies might represent sites of high levels of trends in CELL BIOLOGY (Vol. 8) July 1998
transcriptional activity of particular genes. This is an intriguing and testable concept that once again confirms the emerging view that nuclear structure is crucial for the orchestration of nuclear functions.
Nuclear waste disposal SHIMIZU, N., ITOH, N., UTIYAMA, H. and WAHL, G. (1998) Selective entrapment of extrachromosomally amplified DNA by nuclear budding and micronucleation during S phase J. Cell Biol. 140, 1307–1320 Certain cancer cells accumulate aberrant chromosomal structures, such as circular, autonomously replicating double-minute chromosomes (DMs). The acentric DMs arise at high frequency in cells that have been treated with cytostatic drugs and thus are thought to be responsible for drug-resistant tumours. Wahl and collaborators now present a morphological characterization of a process termed micronucleation that functions in the removal of such aberrant structures from the nucleus. Interestingly, in synchronized tissue-culture cells, the DMs are included into small, membraneenclosed structures that arise from the nuclear envelope during S phase, when the nuclear envelope is intact. This mechanism is a viable alternative to the previously observed nuclear envelope condensation during postmitotic nuclear reassembly that also can result in micronucleus formation. The S-phase-specific micronucleation process seems to be enhanced by treating cells with replication inhibitors, offering a strategy for how to extrude DMs from tumour cells and thus increase their sensitivity to cytostatic drugs. The fact that these micronuclei only form in the presence of DMs predicts that the cell must employ a mechanism to recognize acentric DNA and initiate a series of events that ultimately lead to inclusion of the deviant DNA into a nuclear-envelope-enclosed vesicle. The micronuclei must then be targeted for either extrusion from the cell or internal degradation. Further studies aimed at understanding the signals that induce micronucleation and the molecular mechanism of this important cellular event should unravel an interesting signal-transduction pathway.
Biofilm, starring… DAVIES, D. G., PARSEK, M. R., PEARSON, J. P., IGLEWSKI, B. H., COSTERTON, J. W. and GREENBERG, E. P. (1998) The involvement of cell-to-cell signals in the development of a bacterial biofilm Science 280, 295–298 Most bacteria develop a mechanism for adhering to solid surfaces to establish complex communities known as biofilms. These consist of differentiated mushroom- and
263