Author: Ariana Nakta Samadpour
Publisher:
ISBN:
Category :
Languages : en
Pages : 109
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Book Description
All organisms must control the timing of DNA replication to maintain their genomic stability. In bacteria, this is achieved through tightly controlling the frequency of replication initiation. Though it is well established that DNA topology is important for replication initiation, it was unclear whether the enzymes that modulate supercoiling are important for regulating this process. The work presented in this dissertation identifies a novel role for the essential topoisomerase, DNA gyrase, as a negative regulator of the replication initiator, DnaA. We find that gyrase activity is required for proper binding of DnaA to oriC and controls replication initiation frequency in the model Gram-positive bacterium, Bacillus subtilis. Based on the conservation of both gyrase and DnaA across all bacteria, and the importance of DNA topology for all stages of DNA replication, it is unlikely that this regulatory mechanism is unique to B. subtilis, and likely reflects a general strategy widely utilized by prokaryotes. Creating genetic variability within bacterial populations is important for adaptation and survival. Therefore, cells must balance the need for high fidelity DNA replication with the need for genetic variability. They promote fidelity by accurately copying their DNA and repairing damaged DNA. Cells can increase variability by inducing pathways that introduce mutations. In particular, genome architecture and transcription levels together dictate mutation rates as a result of collisions between DNA replication forks and RNA polymerase. In support of previous work, I found that transcription-coupled nucleotide excision repair facilitates the increased mutation rates of highly transcribed genes in B. subtilis. Furthermore, I found that this mutagenesis is dependent on the activity of DNA polymerase I and the translesion synthesis polymerases YqjH and YqjW. My work contributes to our understanding of transcription-associated mutagenesis.
Author: Bradley Theodore Smith
Publisher:
ISBN:
Category : Press
Languages : en
Pages : 316
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Book Description
All organisms face constant challenges to the integrity of their genomes, from environmental agents such as ultraviolet light (UV) to errors generated by their own DNA polymerases. To deal with these challenges, all organisms possess a range of DNA repair and damage tolerance systems. In bacteria, there exists an inducible response to DNA damage termed the SOS response, in which damage induces the expression of greater than forty genes involved in repair. Mismatch repair (MMR) is a system by which the cell is able to avoid mutations by correcting DNA replication errors. Working with living Bacillus subtilis cells, the studies described here have found that MutS and MutL, the key proteins of MMR, form discrete foci in response to mismatches. These MMR foci are the active sites of repair, and appear to assemble near the DNA polymerase at mismatched base-pairs. This is consistent with a model in which the newly-synthesized DNA strand containing the error is discriminated from the parental strand via interactions between MMR proteins and the replisome.
Author: Monika Glinkowska
Publisher: Springer
ISBN: 3319105337
Category : Science
Languages : en
Pages : 56
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Book Description
This work describes the current knowledge of biochemical mechanisms regulating initiation of DNA replication in Escherichia coli, which focuses on the control of activity of the DnaA protein. Examples of direct linkages between DNA replication and other cellular processes are provided. In addition, similarities of the mechanisms of regulation of DNA replication operating in prokaryotic and eukaryotic cells are identified, and implications for understanding more complex processes, like carcinogenesis are suggested. Studies of recent years provided evidence that regulation of DNA replication in bacteria is more complex than previously anticipated. Multiple layers of control seem to ensure coordination of this process with the increase of cellular mass and the division cycle. Metabolic processes and membrane composition may serve as points where integration of genome replication with growth conditions occurs. It is also likely that coupling of DNA synthesis with cellular metabolism may involve interactions of replication proteins with other macromolecular complexes, responsible for various cellular processes. Thus, the exact set of factors participating in triggering the replication initiation may differ depending on growth conditions. Therefore, understanding the regulation of DNA duplication requires placing this process in the context of the current knowledge on bacterial metabolism, as well as cellular and chromosomal structure. Moreover, in both Escherichia coli and eukaryotic cells, replication initiator proteins were shown to play other roles in addition to driving the assembly of replication complexes, which constitutes another, yet not sufficiently understood, layer of coordinating DNA replication with the cell cycle.
Author: Lilah Lillian Rahn-Lee
Publisher:
ISBN:
Category : DNA replication
Languages : en
Pages : 218
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Book Description
Here, I investigate the regulation of DNA replication during development in B. subtilis. I present evidence that replication is actively inhibited in response to the master regulator of sporulation, SpoOA. I further show that this regulation requires a gene transcribed in the presence of Spo0A, yneE, which I rename sirA, for s[barbelow]porulation i[barbelow]nhibitor of r[barbelow]eplication. The expression of sirA during growth, when it is not usually expressed, results in a growth defect and in the production of cells that lack genetic material. To investigate the mechanism by which sirA inhibits DNA replication, I performed a targeted screen to search for suppressors of sirA expression in the dnaA gene. Four mutations in three amino acids of DnaA allow cells to grow in the presence of SirA. I demonstrate that these residues, which form a patch on the surface of the N-terminal domain of DnaA, make up the interaction site between the DnaA and SirA proteins. Finally, I show that SirA interferes with DnaA's ability to bind the origin of replication.
Author: Alexi I. Goranov
Publisher:
ISBN:
Category :
Languages : en
Pages : 446
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Book Description
(Cont.) My results demonstrate that the conserved recombination protein, RecA, mediates most of the transcriptional response under the tested conditions. More than 75% of the RecA-mediated transcriptional response is due to the expression of phage and mobile element genes and their indirect effects. Under conditions of replication elongation arrest, there is still a significant recA-independent response, at least part of which is mediated by the replication protein DnaA. The DnaA-mediated response appears to be conserved in other bacteria, as homologues if the affected genes also have DnaA binding sites in their promoter regions. Previously, one of the DnaA regulated genes, sda, has been shown to affect cell viability after perturbations in replication. Here I showed that another DnaA-regulated gene, ftsL, also affects cell survival after replication arrest by coordinating replication and cell-division. I believe that my results have furthered our understanding of how replication is coordinated with other cell-cycle processes, and have raised interesting questions for future investigation.
Author: Mary Elizabeth Anderson (Ph. D.)
Publisher:
ISBN:
Category :
Languages : en
Pages : 128
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Book Description
DNA replication is a highly regulated process across all organisms. Improper regulation of DNA replication can be detrimental. I identified an overinitiating, conditional synthetic lethal mutant of Bacillus subtilis. I isolated suppressors of this mutant and uncovered novel genes associated with DNA replication. These suppressors acted both at the steps of initiation and elongation to overcome the detrimental replication initiation of the synthetic lethal [delta]yabA dnaA 1 mutant. One class of suppressors decreased levels of the replicative helicase, DnaC. I showed that decreased levels of helicase are sufficient to limit replication initiation under fast growth conditions. I also explored the regulation of DnaA as a transcription factor. The replication initiation inhibitor, YabA, binds to DnaA and prevents its cooperative binding at the origin. In addition to its role in replication initiation, DnaA also directly regulates expression of several genes. YabA has been shown to inhibit DnaA binding at several promoters but its effect on DnaA-mediated gene expression is unclear. I found that YabA inhibits sda activation by DnaA but does not significantly affect repression of ywlC by DnaA. Lastly, I showed that YabA appears to stimulate autoregulation of dnaA. This preliminary data illustrates a role for YabA regulation in DnaA-mediated gene expression.
Author: Mark M. Zukowski
Publisher: Elsevier
ISBN: 0323150624
Category : Nature
Languages : en
Pages : 432
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Book Description
Genetics and Biotechnology of Bacilli, Volume 3 covers the proceedings of the Fifth International Conference on Genetics and Biotechnology of Bacilli, held on July 9-12, 1989 at the Asilomar Conference Center, Pacific Grove, California. It summarizes the remarkable progress made in the genetics and biotechnology fields of Bacilli. It is organized into four parts, encompassing 43 chapters, which focus on gene regulation and structure, enzyme structure, Bacillus thuringiensis toxins, and stationary phase gene regulation. Part I covers topics related to gene regulation and structure of Bacilli, such as control of gene expression, mutation, genetic organization, DNA sequence analysis, and identification of transcript units. It also discusses gene replication in Bacillus subtilis plasmids, levanase operon of B. subtilis, and characterization of global regulon in B. subtilis. The next part of this book focuses on the structure of various enzymes found in B. subtilis, including alpha amylases, subtilisin, alkaline phosphatase, and levansucrase. Part III discusses the generation of functional B. thuringiensis toxin hybrid genes, regulation of crystal protein gene promoters, toxicity of B. thuringiensis delta-endotoxin, and insecticidal activity of chimeric protoxins. The concluding part covers the aspects of signal transduction, regulation of differential gene expression during B. subtilis sporulation, and gene cloning and deletion for extracellular proteases of B. subtilis. It also discusses genetic and biochemical aspects of protein phosphorylation; properties of B. subtilis spores; control of stationary phase gene expression; and the novel regulatory gene, senS, of B. subtilis. This book is a valuable source of information for microbiologists, research biologists, and Bacilli enthusiasts.
Author: June Jenny Andersen
Publisher:
ISBN:
Category :
Languages : en
Pages : 360
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Book Description
Author: Patricia M. Benjamin
Publisher:
ISBN:
Category : Bacillus subtilis
Languages : en
Pages : 168
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Book Description
Author: Jan Löwe
Publisher: Springer
ISBN: 331953047X
Category : Science
Languages : en
Pages : 457
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Book Description
This book describes the structures and functions of active protein filaments, found in bacteria and archaea, and now known to perform crucial roles in cell division and intra-cellular motility, as well as being essential for controlling cell shape and growth. These roles are possible because the cytoskeletal and cytomotive filaments provide long range order from small subunits. Studies of these filaments are therefore of central importance to understanding prokaryotic cell biology. The wide variation in subunit and polymer structure and its relationship with the range of functions also provide important insights into cell evolution, including the emergence of eukaryotic cells. Individual chapters, written by leading researchers, review the great advances made in the past 20-25 years, and still ongoing, to discover the architectures, dynamics and roles of filaments found in relevant model organisms. Others describe one of the families of dynamic filaments found in many species. The most common types of filament are deeply related to eukaryotic cytoskeletal proteins, notably actin and tubulin that polymerise and depolymerise under the control of nucleotide hydrolysis. Related systems are found to perform a variety of roles, depending on the organisms. Surprisingly, prokaryotes all lack the molecular motors associated with eukaryotic F-actin and microtubules. Archaea, but not bacteria, also have active filaments related to the eukaryotic ESCRT system. Non-dynamic fibres, including intermediate filament-like structures, are known to occur in some bacteria.. Details of known filament structures are discussed and related to what has been established about their molecular mechanisms, including current controversies. The final chapter covers the use of some of these dynamic filaments in Systems Biology research. The level of information in all chapters is suitable both for active researchers and for advanced students in courses involving bacterial or archaeal physiology, molecular microbiology, structural cell biology, molecular motility or evolution. Chapter 3 of this book is open access under a CC BY 4.0 license.
