Control of M-G1 phase-specific expression in fission yeast

Control of M-G1 phase-specific expression in fission yeast
Author :
Publisher :
Total Pages : 299
Release :
ISBN-10 : OCLC:757045438
ISBN-13 :
Rating : 4/5 (38 Downloads)

Synopsis Control of M-G1 phase-specific expression in fission yeast by : Kyriaki Papadopoulou

The mitotic cell cycle underlies propagation of eukaryotic cells, continually duplicating and dividing. The past few years have seen major advances in understanding of the regulatory mechanisms that impose on the cell cycle to tightly co-ordinate progression through its individual phases, safeguarding the timing and integrity of its hallmark events, DNA synthesis and mitosis. Transcription is prominent among these processes, manifesting its importance for cell cycle controls by the large number of eukaryotic genes that are expressed at specific cell cycle times. Certain genes are cell cycle regulated in a number of organisms, suggesting that their phase-specific transcription is important for all eukaryotic cells. The budding and fission yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, have been used extensively as model organisms for the study of the eukaryotic cell cycle and cell cycle-regulated transcription, because the cell cycle machinery is conserved among eukaryotes and they are experimentally tractable. Recent microarray analyses have shown that cell cycle-specific expression is a frequent theme in the two yeasts, identifying consecutive, inter-dependent, waves of transcriptional activity, coinciding with the four main cell cycle transitions; G1-S, S, G2-M and M-G1 phases. Each phase-specific transcriptional wave corresponds to at least one group of co-regulated genes, sharing common cis- and trans- acting elements. The work presented in this thesis delves into the regulatory network that drives phase-specific gene expression during late mitosis-early G1 phase in fission yeast. During this late cell cycle stage, fission yeast and, indeed, every eukaryotic cell, undergo major changes; each completes mitosis and cytokinesis, partitioning its duplicated genetic and cytoplasmic material into two progeny cells, which then themselves prepare for a new round of mitotic cell division. Consistent with their periodic pattern of expression, most of the genes transcribed during the M-G1 interval in S. pombe encode proteins that execute important functions during late mitosis and cytokinesis. A DNA sequence promoter motif, the PCB (Pombe cell cycle box), has been identified in fission yeast that confers M-G1 specific transcription, and is bound by the PBF (PCB binding factor) transcription factor complex. PCB promoter motifs are present in several M-G1 transcribed genes, including cdc15, spo12, sid2+, fin1+, slp1+, ace2+, mid1+/dmf1+ and plo1+, the latter encoding a Polo-like kinase that also regulates M-G1 gene expression and influences the PCB-dependent binding properties of PBF. Three transcription factors, Sep1p and Fkh2p, both forkhead-like transcription factors, and Mbx1p, a MADS-box protein, have been implicated in M-G1 specific gene expression and are thought to be components of PBF. Consistent with Fkh2p and Sep1p regulating M-G1 specific transcription, forkhead-related sequences are present in the genes' promoters. Notably, fkh2+ contains both PCB and forkhead promoter sequences and is transcribed during the M-G1 interval, implying that Fkh2p and Plo1p regulate gene transcription during late mitosis and ensuing passage through cytokinesis via feedback loops. This study provides further evidence about transcriptional regulation late in the fission yeast cell cycle, revealing that the PCB sequence is crucial for M-G1 specific transcription, with forkhead-associated DNA motifs playing a parallel but smaller regulatory role. Consistent with this hypothesis, work here and elsewhere shows that both Fkh2p and Sep1p control phase-specific expression of their co-regulated genes through the PCB and forkhead sequences. Notably, data in this thesis reveal that these two forkhead transcription factors associate with each other in vitro and in vivo and bind in vivo to the PCB promoter regions of M-G1 transcribed genes, including cdc15+ and plo1+, in a cell cycle specific manner, consistent with Fkh2p repressing and Sep1p activating transcription. Furthermore, Fkh2p contacts its own promoter, suggesting that it regulates its own expression via a negative feedback mechanism. The Plo1p kinase is shown here to bind in vivo to Mbx1p throughout the cell cycle and in a manner that requires both its kinase and polo-box domains. In agreement with this observation, Plo1p can phosphorylate in vitro Mbx1p, itself known to become phosphorylated during late mitosis. This is the first time that a Polo-like kinase has been shown to bind and phosphorylate a MADS-box protein in any organism. Moreover, in concert with Plo1p binding and phosphorylating Mbx1p, ChIP assays here reveal that this kinase interacts in vivo with the PCB promoter DNA of M-G1 expressed genes, including cdc15+ and fkh2+, in a cell cycle-dependent manner with a timing that coincides with low levels of expression, but follows promoter binding by Fkh2p. Given that Plo1p has previously been shown to positively influence M-G1 dependent transcription, its cell cycle pattern of promoter contact suggests that this Polo-like kinase functions at the genes' promoters, most-likely via binding and phosphorylation of Mbx1p, to re-stimulate transcription, following repression by Fkh2p. In parallel, these findings suggest that Plo1p regulates its own expression via a positive feedback loop. Overall, the work presented in this thesis unravels crucial regulatory aspects of the transcriptional network that drives M-G1 specific transcription in S. pombe: it suggests an important role for the PCB promoter motif in transcriptional regulation; it proposes that Fkh2p acts as a repressor while Sep1p as an activator of late mitotic transcription; it reveals and proposes novel functions for Plo1p, a conserved Polo-like kinase family member, involving its association with Mbx1p, a MADS box protein, and its cell cycle specific recruitment to PCB promoters of M-G1 transcribed genes. As transcriptional systems, encompassing homologues of most of the components of this S. pombe M-G1 specific transcriptional network operate both in S. cerevisiae and humans, this demonstrates their importance for mitotic cell cycle progression. Thus this work potentially offers new insights into M-G1 specific gene expression in all eukaryotes.

The Plant Cell Cycle

The Plant Cell Cycle
Author :
Publisher : Springer Science & Business Media
Total Pages : 240
Release :
ISBN-10 : 9789401009362
ISBN-13 : 9401009368
Rating : 4/5 (62 Downloads)

Synopsis The Plant Cell Cycle by : Dirk Inzé

In recent years, the study of the plant cell cycle has become of major interest, not only to scientists working on cell division sensu strictu , but also to scientists dealing with plant hormones, development and environmental effects on growth. The book The Plant Cell Cycle is a very timely contribution to this exploding field. Outstanding contributors reviewed, not only knowledge on the most important classes of cell cycle regulators, but also summarized the various processes in which cell cycle control plays a pivotal role. The central role of the cell cycle makes this book an absolute must for plant molecular biologists.

Cell Cycle Regulation

Cell Cycle Regulation
Author :
Publisher : Results and Problems in Cell Differentiation
Total Pages : 400
Release :
ISBN-10 : UVA:X030151344
ISBN-13 :
Rating : 4/5 (44 Downloads)

Synopsis Cell Cycle Regulation by : Philipp Kaldis

This book is a state-of-the-art summary of the latest achievements in cell cycle control research with an outlook on the effect of these findings on cancer research. The chapters are written by internationally leading experts in the field. They provide an updated view on how the cell cycle is regulated in vivo, and about the involvement of cell cycle regulators in cancer.

Molecular Genetics of Recombination

Molecular Genetics of Recombination
Author :
Publisher : Springer Science & Business Media
Total Pages : 536
Release :
ISBN-10 : 9783540710219
ISBN-13 : 3540710213
Rating : 4/5 (19 Downloads)

Synopsis Molecular Genetics of Recombination by : Andrés Aguilera

This work offers a fascinating insight into a crucial genetic process. Recombination is, quite simply, one of the most important topics in contemporary biology. This book is a totally comprehensive treatment of the subject, summarizing all existing views on the topic and at the same time putting them into context. It provides in-depth and up-to-date analysis of the chapter topics, and has been written by international experts in the field.

Progress in Cell Cycle Research

Progress in Cell Cycle Research
Author :
Publisher : Springer Science & Business Media
Total Pages : 245
Release :
ISBN-10 : 9781461542537
ISBN-13 : 1461542537
Rating : 4/5 (37 Downloads)

Synopsis Progress in Cell Cycle Research by : Laurent Meijer

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.

The Biology of the Cell Cycle

The Biology of the Cell Cycle
Author :
Publisher : CUP Archive
Total Pages : 324
Release :
ISBN-10 : 052108251X
ISBN-13 : 9780521082518
Rating : 4/5 (1X Downloads)

Synopsis The Biology of the Cell Cycle by : J. M. Mitchison

The Cell Cycle

The Cell Cycle
Author :
Publisher : New Science Press
Total Pages : 328
Release :
ISBN-10 : 9780878935086
ISBN-13 : 0878935088
Rating : 4/5 (86 Downloads)

Synopsis The Cell Cycle by : David Owen Morgan

The Cell Cycle: Principles of Control provides an engaging insight into the process of cell division, bringing to the student a much-needed synthesis of a subject entering a period of unprecedented growth as an understanding of the molecular mechanisms underlying cell division are revealed.

Yeast

Yeast
Author :
Publisher : John Wiley & Sons
Total Pages : 1
Release :
ISBN-10 : 9783527659197
ISBN-13 : 3527659196
Rating : 4/5 (97 Downloads)

Synopsis Yeast by : Horst Feldmann

Finally, a stand-alone, all-inclusive textbook on yeast biology. Based on the feedback resulting from his highly successful monograph, Horst Feldmann has totally rewritten he contents to produce a comprehensive, student-friendly textbook on the topic. The scope has been widened, with almost double the content so as to include all aspects of yeast biology, from genetics via cell biology right up to biotechnology applications. The cell and molecular biology sections have been vastly expanded, while information on other yeast species has been added, with contributions from additional authors. Naturally, the illustrations are in full color throughout, and the book is backed by a complimentary website. The resulting textbook caters to the needs of an increasing number of students in biomedical research, cell and molecular biology, microbiology and biotechnology who end up using yeast as an important tool or model organism.