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Molecular regulation of nuclear events in mitosis and meiosis
72
TIBS 13-February 1988
Towards a unified theow of cell-cycle regulation? Molecular Regulation of Nuclear Events in Mitosis and Meiosis edited by Robert A. Schlegel, Margaret S. Halleck and Potu N. Rao, Academic Press, 1987. $85.00/£71.00 (xii + 375 pages) ISBN 0 12 625115 0
Extensive reorganization of nuclear structures occurs at meiosis in germ-line cells and during mitosis in the somatic cell cycle. We are all aware of the gross features of chromatin condensation and decondensation, of spindle assembly and chromosome segregation, and of the breakdown and reformation (at least in higher eukaryotes) of the nuclear envelope (NE). But how can these dynamic processes be explained at the molecular level and how can we set about identifying the regulatory factors which determine their onset and completion? This volume sets out to present a state-of-the-art account of research into these questions. Coverage breaks down into approximately two halves, the first six chapters deaiing with largely meiotic events, the last five chapters with mitotic events. However, this is no hard-and-fast distinction: as pointed out throughout the book, meiotic and mitotic regulatory factors are often interchangeable, giving some sense of unification to the different contributions. Not surprisingly, much of the work on meiosis exploits the large and easilyobtained oocytes and eggs of amphibia. Chapter 1, by Masui and Shibuya presents a valuable historical perspective and definition of components involved in oocytc maturation. Although the main structural components of the nucleus are fairly well understood in terms of their molecular constitution, the cytoplasmic regulatory factors are still defined operationally as, for example, maturation promoting factor (MPF), cytostatic factor (CSF), chromosome condensation factor (CCF), chromosome decondensation factor (CDF). It can only be hoped that in the not-to-distant future some biochemical identity can be given to these agents. As the book makes clear, the favoured causal pathway is that the cytoplasmic regulatory factors initiate modification of nuclear proteins which then brings about reorganization of nuclear structures. Major events in reorganization are identified as membrane dissolution, breakdown of the nuclear lamina and chromosome condensation. Indeed, recently, these processes have been
shown to represent three independent responses I.
Much impetus for contemporary research on the mechanisms involved derives from an increasing understanding of the chemical structure of nuclear proteins and from the development of in vitro systems for the study of nuclear assembly/disassembly. The two approaches receive adequate coverage here. Chapter 2, by Stick, outlines the elegant immunostaining analysis of the nuclear lamina, a protein lining on the innermost surface of the nuclear membrane, which breaks down and reforms during the mitotic cell cycle. Since the lamina may provide a framework not only for the nuclear envelope, but also for the arrangement of interphase chromatin, the dynamics of laminar assembly/disassembly (probably through reversible phosphorylation) are central to an understanding of many aspects of nuclear organization. The recent finding that the laminar proteins (lamins) are structurally homologous to cytoplasmic intermediate filament proteins (see Ref. 2 for review) may lead to a more general theory of intracellular structuring. Chapter 11, by Yasuda et al., presents a lucid account of histone modifications and the role they play in chromatin condensation/decondensation through mitosis. Specifically, this chapter deals with patterns of phosphorylation, acetylation and ubiquitination during the cell cycle of a simple model organism Physarum polycephalum. Not only histones and lamins, but a whole range of nuclear and cytoplasmic proteins are phosphorylated at mitosis. In Chapter 9, Davis and Rao describe their systematic use of monodonal antibodies specific to cells in mitosis to identify (phospho)proteins active in chromatin condensation and in reorganization of cytoskeletal components to form the spindle. Nishimoto et al. (Chapter 10) make use of a mutant cell line with a temperature-sensitive lesion (tsBN2) in studies on the regulation of chromatin condensation. This they equate with a failure to inhibit activation of protein kinase, leading to premature chromatin condensation through protein phosphorylation. Analogies are drawn with comparable mutant phenotypes in yeast. It is a pity that so little mention is made elsewhere in the book of the major contribution to our understanding of cellcycle control made by the study of mutant yeasts.
The development of systems to reconstruct a nuclear envelope around chromatin made great advances with the observations of Forbes et al. 3 that purified lambda DNA injected into Xenopus eggs induces the spontaneous formation of mininuclei, and with the development of an in vitro system from Rana eggs which reconstitutes a nuclear envelope around demembranatedsperm nuclei. This latter work is extended in Chapter 3, by Lohka and Mailer who use cytoplasmic extracts from unactivated eggs to identify maturation promoting factor preparations as the controlling agents for nuclear-envelope breakdown, chromatin condensation and spindle formation and Ca 2+ ions as potential regulatory factors for nuclear-envelope assembly and chromosome decondensation. In similar studies, Poccia (Chapter 6) sets about to define the conditions for chromatin condensation/decondensation in the sperm pronuclei of sea urchins. In these and all other chapters, the role of protein phosphorylation is given centre stage. To complete the scheme the relevant protein kinases (for instance with activities of the type described by Halleck et al., in Chapter 8) may well be purified from the maturation and mitosis-inducing extracts in the next few years. However, one wonders if the accent on phosphorylation is mainly vogue and if other protein modifications may turn out to be equally important in cell-cycle regulation. In general, all chapters in this book are informative and clearly presented. With the proviso that more recent advances (since 1986) are not recorded, purchase of the book for libraries and for workers in related fields is recommended. References 1 Newport, J. and Spann, T. (1987) Ce!!48,219230 2 Franke, W. W. (1987) Ceil48, 3-4 3 Forbes, D. J., Kirschner, M. W. and Newport, J. W. (1983) Cell34, 13-23 JOHN SOMMERVILLE
Department of Biology, Universityof St Andrews, St Andrews, F(feKYI6 9TS, UK.
TIBS 13-February 1988
Towards a unified theow of cell-cycle regulation? Molecular Regulation of Nuclear Events in Mitosis and Meiosis edited by Robert A. Schlegel, Margaret S. Halleck and Potu N. Rao, Academic Press, 1987. $85.00/£71.00 (xii + 375 pages) ISBN 0 12 625115 0
Extensive reorganization of nuclear structures occurs at meiosis in germ-line cells and during mitosis in the somatic cell cycle. We are all aware of the gross features of chromatin condensation and decondensation, of spindle assembly and chromosome segregation, and of the breakdown and reformation (at least in higher eukaryotes) of the nuclear envelope (NE). But how can these dynamic processes be explained at the molecular level and how can we set about identifying the regulatory factors which determine their onset and completion? This volume sets out to present a state-of-the-art account of research into these questions. Coverage breaks down into approximately two halves, the first six chapters deaiing with largely meiotic events, the last five chapters with mitotic events. However, this is no hard-and-fast distinction: as pointed out throughout the book, meiotic and mitotic regulatory factors are often interchangeable, giving some sense of unification to the different contributions. Not surprisingly, much of the work on meiosis exploits the large and easilyobtained oocytes and eggs of amphibia. Chapter 1, by Masui and Shibuya presents a valuable historical perspective and definition of components involved in oocytc maturation. Although the main structural components of the nucleus are fairly well understood in terms of their molecular constitution, the cytoplasmic regulatory factors are still defined operationally as, for example, maturation promoting factor (MPF), cytostatic factor (CSF), chromosome condensation factor (CCF), chromosome decondensation factor (CDF). It can only be hoped that in the not-to-distant future some biochemical identity can be given to these agents. As the book makes clear, the favoured causal pathway is that the cytoplasmic regulatory factors initiate modification of nuclear proteins which then brings about reorganization of nuclear structures. Major events in reorganization are identified as membrane dissolution, breakdown of the nuclear lamina and chromosome condensation. Indeed, recently, these processes have been
shown to represent three independent responses I.
Much impetus for contemporary research on the mechanisms involved derives from an increasing understanding of the chemical structure of nuclear proteins and from the development of in vitro systems for the study of nuclear assembly/disassembly. The two approaches receive adequate coverage here. Chapter 2, by Stick, outlines the elegant immunostaining analysis of the nuclear lamina, a protein lining on the innermost surface of the nuclear membrane, which breaks down and reforms during the mitotic cell cycle. Since the lamina may provide a framework not only for the nuclear envelope, but also for the arrangement of interphase chromatin, the dynamics of laminar assembly/disassembly (probably through reversible phosphorylation) are central to an understanding of many aspects of nuclear organization. The recent finding that the laminar proteins (lamins) are structurally homologous to cytoplasmic intermediate filament proteins (see Ref. 2 for review) may lead to a more general theory of intracellular structuring. Chapter 11, by Yasuda et al., presents a lucid account of histone modifications and the role they play in chromatin condensation/decondensation through mitosis. Specifically, this chapter deals with patterns of phosphorylation, acetylation and ubiquitination during the cell cycle of a simple model organism Physarum polycephalum. Not only histones and lamins, but a whole range of nuclear and cytoplasmic proteins are phosphorylated at mitosis. In Chapter 9, Davis and Rao describe their systematic use of monodonal antibodies specific to cells in mitosis to identify (phospho)proteins active in chromatin condensation and in reorganization of cytoskeletal components to form the spindle. Nishimoto et al. (Chapter 10) make use of a mutant cell line with a temperature-sensitive lesion (tsBN2) in studies on the regulation of chromatin condensation. This they equate with a failure to inhibit activation of protein kinase, leading to premature chromatin condensation through protein phosphorylation. Analogies are drawn with comparable mutant phenotypes in yeast. It is a pity that so little mention is made elsewhere in the book of the major contribution to our understanding of cellcycle control made by the study of mutant yeasts.
The development of systems to reconstruct a nuclear envelope around chromatin made great advances with the observations of Forbes et al. 3 that purified lambda DNA injected into Xenopus eggs induces the spontaneous formation of mininuclei, and with the development of an in vitro system from Rana eggs which reconstitutes a nuclear envelope around demembranatedsperm nuclei. This latter work is extended in Chapter 3, by Lohka and Mailer who use cytoplasmic extracts from unactivated eggs to identify maturation promoting factor preparations as the controlling agents for nuclear-envelope breakdown, chromatin condensation and spindle formation and Ca 2+ ions as potential regulatory factors for nuclear-envelope assembly and chromosome decondensation. In similar studies, Poccia (Chapter 6) sets about to define the conditions for chromatin condensation/decondensation in the sperm pronuclei of sea urchins. In these and all other chapters, the role of protein phosphorylation is given centre stage. To complete the scheme the relevant protein kinases (for instance with activities of the type described by Halleck et al., in Chapter 8) may well be purified from the maturation and mitosis-inducing extracts in the next few years. However, one wonders if the accent on phosphorylation is mainly vogue and if other protein modifications may turn out to be equally important in cell-cycle regulation. In general, all chapters in this book are informative and clearly presented. With the proviso that more recent advances (since 1986) are not recorded, purchase of the book for libraries and for workers in related fields is recommended. References 1 Newport, J. and Spann, T. (1987) Ce!!48,219230 2 Franke, W. W. (1987) Ceil48, 3-4 3 Forbes, D. J., Kirschner, M. W. and Newport, J. W. (1983) Cell34, 13-23 JOHN SOMMERVILLE
Department of Biology, Universityof St Andrews, St Andrews, F(feKYI6 9TS, UK.