Progress in Cell Cycle Research is a new annual series designed to be the source for up-to-date research on this rapidly expanding field. Review articles by international experts examine various aspects of cell division regulation from fundamental perspectives to potential medical applications. Researchers as well as advanced undergraduate and graduate students in cell biology, biochemistry, and molecular biology will benefit from this series.

When used in the context of reproduction of living cells the phrase "cell growth" is shorthand for the idea of "growth in cell populations by means of cell reproduction." During cell reproduction one cell (the "mother" cell) divides to produce two daughter cells. Cell proliferation, which depends on the intimately linked processes of growth and division, is a fundamental systems-level attribute of all life forms. The precise regulation of proliferation in response to internal and external cues is critical for development, tissue renewal and evolutionary fitness, while the disregulation of cell proliferation underlies a variety of human diseases, most notably cancer and ageing. Historically, breakthroughs in our understanding of cell growth and division have derived from cross-fertilisation of results and ideas from researchers studying a wide range of model organisms, from yeast to humans. The basis for cell proliferation entails the control of key signalling and cell cycle regulators through transcriptional, translational, post-translational, genetic and epigenetic mechanisms. Indeed, many conceptual breakthroughs in cell regulation have derived from analyses of basic cell cycle mechanisms. This book is dedicated to new research from around the globe in this field.

The latest volume in this highly regarded series covers current advances in the fast-moving field of cell cycle research by gathering reviews otherwise scattered throughout the literature. Contributions encompass fields from cell and molecular biology to biochemistry.

Now in its second year, Progress in Cell Cycle Research was conceived to serve as an up to date introduction to various aspects of the cell division cycle. Although an annual review in any field of scientific investigation can never be as current as desired, especially in the cell cycle field, we hope that this volume will be helpful to students, to recent graduates considering a de1liation in subject and to investigators at the fringe of the cell cycle field wishing to bridge frontiers. An instructive approach to many subjects in biology is often to make comparisons between evolutionary distant organisms. If one is willing to accept that yeast represent a model primitive eukaryote, then it is possible to make some interesting comparisons of cell cycle control mechanisms between mammals and our little unicellular cousins. By and large unicellular organisms have no need for intracellular communication. With the exception of the mating phenomenon in S. cerevisiae and perhaps some nutritional sensing mechanisms, cellular division of yeast proceeds with complete disregard for neighbourly communication. Multicellular organisms on the other hand, depend entirely on intracellular communication to maintain structural integrity. Consequently, elaborate networks have evolved to either prevent or promote appropriate cell division in multicellular organisms. Yet, as described in chapter two the rudimentary mechanisms for fine tuning the cell division cycle in higher eukaryotes are already apparent in yeast.

The "Progress in Cell Cycle Research" series is dedicated to serve as a collection of reviews on various aspects of the cell division cycle, with special emphasis on less studied aspects. We hope this series will continue to be helpful to students, graduates and researchers interested in the cell cycle area and related fields. We hope that reading of these chapters will constitute a "point of entry" into specific aspects of this vast and fast moving field of research. As PCCR4 is being printed several other books on the cell cycle have appeared (ref. 1-3) which should complement our series. This fourth volume of PCCR starts with a review on RAS pathways and how they impinge on the cell cycle (chapter 1). In chapter 2, an overview is presented on the links between cell anchorage -cytoskeleton and cell cycle progression. A model of the Gl control in mammalian cells is provided in chapter 3. The role of histone acetylation and cell cycle contriol is described in chapter 4. Then follow a few reviews dedicated to specific cell cycle regulators: the 14-3-3 protein (chapter 5), the cdc7/Dbf4 protein kinase (chapter 6), the two products of the pI6/CDKN2A locus and their link with Rb and p53 (chapter 7), the Ph085 cyclin-dependent kinases in yeast (chapter 9), the cdc25 phophatase (chapter 10), RCCI and ran (chapter 13). The intriguing phosphorylation dependent prolyl-isomerization process and its function in cell cycle regulation are reviewed in chapter 8.