scholarly journals Mechanical Properties of DNA Replication

2019 ◽  
Author(s):  
Stuart A. Sevier
Keyword(s):  
Mechanical Properties ◽  
Dna Replication ◽  
Helical Structure ◽  
Physical Basis ◽  
Replication Process ◽  
Idealized Model ◽  
Cellular Life ◽  
Gene Orientation ◽  
Mechanical Elements

Central to the function of cellular life is the reading, storage and replication of DNA. Due to the helical structure of DNA, a complicated topological braiding of new strands follows the duplication of the old strands. Even though this was discovered over 60 years ago, the mathematical and physical questions this presents have largely gone unaddressed. In this letter we construct a simple idealized model of DNA replication using only the most basic mathematical and mechanical elements of DNA replication. The aim of this is to reveal the mechanical balance of braided, replicated DNA against the twist of unreplicated DNA at the heart of the replication process. The addition of topoisomerase action is included presenting a balancing force offering a glimpse into the ways in which cells maintain this balance. Additionally the physical basis for recently observed replication/replication and replication/transcription conflicts are examined showing how gene orientation and size can impact DNA replication.

scholarly journals Diversity of the DNA Replication System in theArchaeaDomain

Archaea ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Felipe Sarmiento ◽  
Feng Long ◽  
Isaac Cann ◽  
William B. Whitman
Keyword(s):  
Information Processing ◽  
Dna Replication ◽  
Cellular Structure ◽  
General Pattern ◽  
Replication Proteins ◽  
Replication Process ◽  
Replication System ◽  
Cellular Life ◽  
Complex Process ◽  
Domains Of Life

The precise and timely duplication of the genome is essential for cellular life. It is achieved by DNA replication, a complex process that is conserved among the three domains of life. Even though the cellular structure of archaea closely resembles that of bacteria, the information processing machinery of archaea is evolutionarily more closely related to the eukaryotic system, especially for the proteins involved in the DNA replication process. While the general DNA replication mechanism is conserved among the different domains of life, modifications in functionality and in some of the specialized replication proteins are observed. Indeed,Archaeapossess specific features unique to this domain. Moreover, even though the general pattern of the replicative system is the same in all archaea, a great deal of variation exists between specific groups.

Atomistic to Continuum Modeling of DNA Molecules

2010 ◽  
Author(s):  
C. H. Lee ◽  
H. Teng ◽  
J. S. Chen
Keyword(s):  
Mechanical Properties ◽  
Helical Structure ◽  
Confined Space ◽  
Dna Molecules ◽  
Continuum Modeling ◽  
Replication Process ◽  
Double Helical Structure ◽  
Biological Implication

The mechanical properties of DNA has very important biological implication. For example, the bending and twisting rigidities of DNA affect how it wraps around histones to form chromosomes, bends upon interactions with proteins, supercoils during replication process, and packs into the confined space within a virus. Many biologically important processes involving DNA are accompanied by the deformations of double helical structure of DNA.

scholarly journals Efficient, quick and easy-to-use DNA replication timing analysis with START-R suite

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Djihad Hadjadj ◽  
Thomas Denecker ◽  
Eva Guérin ◽  
Su-Jung Kim ◽  
Fabien Fauchereau ◽  
...  
Keyword(s):  
Dna Replication ◽  
Cell Fate ◽  
Web Application ◽  
Timing Analysis ◽  
Mutant Cell ◽  
Replication Timing ◽  
Experimental Conditions ◽  
Replication Process ◽  
Time Required ◽  
Dna Replication Timing

Abstract DNA replication must be faithful and follow a well-defined spatiotemporal program closely linked to transcriptional activity, epigenomic marks, intranuclear structures, mutation rate and cell fate determination. Among the readouts of the spatiotemporal program of DNA replication, replication timing analyses require not only complex and time-consuming experimental procedures, but also skills in bioinformatics. We developed a dedicated Shiny interactive web application, the START-R (Simple Tool for the Analysis of the Replication Timing based on R) suite, which analyzes DNA replication timing in a given organism with high-throughput data. It reduces the time required for generating and analyzing simultaneously data from several samples. It automatically detects different types of timing regions and identifies significant differences between two experimental conditions in ∼15 min. In conclusion, START-R suite allows quick, efficient and easier analyses of DNA replication timing for all organisms. This novel approach can be used by every biologist. It is now simpler to use this method in order to understand, for example, whether ‘a favorite gene or protein’ has an impact on replication process or, indirectly, on genomic organization (as Hi-C experiments), by comparing the replication timing profiles between wild-type and mutant cell lines.

Effect of inhibitors of DNA replication on early zebrafish embryos: evidence for coordinate activation of multiple intrinsic cell-cycle checkpoints at the mid-blastula transition

Zygote ◽  
1997 ◽  
Vol 5 (2) ◽  
pp. 153-175 ◽  
Author(s):  
Richard Ikegami ◽  
Alma K. Rivera-Bennetts ◽  
Deborah L. Brooker ◽  
Thomas D. Yager
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Adaptive Response ◽  
Topoisomerase I ◽  
Topoisomerase Ii ◽  
Cell Cycle Checkpoints ◽  
Zebrafish Embryos ◽  
Replication Process ◽  
Inhibition Of Dna Synthesis

SummaryWe address the developmental activation, in the zebrafish embryo, of intrinsic cell-cycle checkpoints which monitor the DNA replication process and progression through the cell cycle. Eukaryotic DNA replication is probably carried out by a multiprotein complex containing numerous enzymes and accessory factors that act in concert to effect processive DNA synthesis (Applegren, N. et al. (1995) J. Cell. Biochem. 59, 91–107). We have exposed early zebrafish embryos to three chemical agents which are predicted to specifically inhibit the DNA polymerase α, topoisomerase I and topoisomerase II components of the DNA replication complex. We present four findings: (1) Before mid-blastula transition (MBT) an inhibition of DNA synthesis does not block cells from attempting to proceed through mitosis, implying the lack of functional checkpoints. (2) After MBT, the embryo displays two distinct modes of intrinsic checkpoint operation. One mode is a rapid and complete stop of cell division, and the other is an ‘adaptive’ response in which the cell cycle continues to operate, perhaps in a ‘repair’ mode, to generate daughter nuclei with few visible defects. (3) The embryo does not display a maximal capability for the ‘adaptive’ response until several hours after MBT, which is consistent with a slow rranscriptional control mechanism for checkpoint activation. (4) The slow activation of checkpoints at MBT provides a window of time during which inhibitors of DNA synthesis will induce cytogenetic lesions without killing the embryo. This could be useful in the design of a deletion-mutagenesis strategy.

scholarly journals Two essential replicative DNA polymerases exchange dynamically during DNA replication and after replication fork arrest

2018 ◽  
Author(s):  
Yilai Li ◽  
Ziyuan Chen ◽  
Lindsay A. Matthews ◽  
Lyle A. Simmons ◽  
Julie S. Biteen
Keyword(s):  
Dna Replication ◽  
Single Molecule ◽  
Replication Fork ◽  
Dna Polymerases ◽  
Super Resolution ◽  
Clamp Loader ◽  
Chromosomal Dna ◽  
Chromosomal Replication ◽  
Replication Process ◽  
Cooperative Process

AbstractThe replisome is the multi-protein complex responsible for faithful replication of chromosomal DNA. Using single-molecule super-resolution imaging, we characterized the dynamics of three replisomal proteins in liveBacillus subtiliscells: the two replicative DNA polymerases, PolC and DnaE, and a processivity clamp loader subunit, DnaX. We quantified the protein mobility and dwell times during normal replication and following both damage-independent and damage-dependent replication fork stress. With these results, we report the dynamic and cooperative process of DNA replication based on changes in the measured diffusion coefficients and dwell times. These experiments show that the replisomal proteins are all highly dynamic and that the exchange rate depends on whether DNA synthesis is active or arrested. Our results also suggest coupling between PolC and DnaX in the DNA replication process, and indicate that DnaX provides an important role in synthesis during repair. Furthermore, our results show that DnaE provides a limited contribution to chromosomal replication and repair.

scholarly journals Properties of Gene Expression and Chromatin Structure with Mechanically Regulated Transcription

2018 ◽  
Author(s):  
Stuart A. Sevier ◽  
Herbert Levine
Keyword(s):  
Gene Expression ◽  
Mechanical Properties ◽  
Dna Structure ◽  
Genetic System ◽  
Dna Supercoiling ◽  
Simple Description ◽  
Gene Orientation ◽  
Physical Elements ◽  
Transcriptional Bursting ◽  
The Impact

The mechanical properties of transcription have emerged as central elements in our understanding of gene expression. Recent work has been done introducing a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase (RNAP) rotation and DNA supercoiling are coupled [1]. Here we generalize this framework to accommodate the behavior of many RNAPs operating on multiple genes on a shared piece of DNA. The resulting framework is combined with well-established stochastic processes of transcription resulting in a model which characterizes the impact of the mechanical properties of transcription on gene expression and DNA structure. Transcriptional bursting readily emerges as a common phenomenon with origins in the geometric nature of the genetic system and results in the bounding of gene expression statistics. Properties of a multiple gene system are examined with special attention paid to role that genome composition (gene orientation, size, and intergenic distance) plays in the ability of genes to transcribe. The role of transcription in shaping DNA structure is examined and the possibility of transcription driven domain formation is discussed.PACS numbers:

scholarly journals Human Exonuclease 1 (EXO1) Regulatory Functions in DNA Replication with Putative Roles in Cancer

2018 ◽  
Vol 20 (1) ◽  
pp. 74 ◽  
Author(s):  
Guido Keijzers ◽  
Daniela Bakula ◽  
Michael Petr ◽  
Nils Madsen ◽  
Amanuel Teklu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Dna Replication ◽  
Replication Fork ◽  
Cellular Transformation ◽  
Cell Cycle Checkpoints ◽  
Replication Process ◽  
Exonuclease 1 ◽  
Repair Pathways ◽  
Regulatory Functions

Human exonuclease 1 (EXO1), a 5′→3′ exonuclease, contributes to the regulation of the cell cycle checkpoints, replication fork maintenance, and post replicative DNA repair pathways. These processes are required for the resolution of stalled or blocked DNA replication that can lead to replication stress and potential collapse of the replication fork. Failure to restart the DNA replication process can result in double-strand breaks, cell-cycle arrest, cell death, or cellular transformation. In this review, we summarize the involvement of EXO1 in the replication, DNA repair pathways, cell cycle checkpoints, and the link between EXO1 and cancer.

Computational prediction and interpretation of cell-specific replication origin sites from multiple eukaryotes by exploiting stacking framework

2020 ◽  
Author(s):  
Leyi Wei ◽  
Wenjia He ◽  
Adeel Malik ◽  
Ran Su ◽  
Lizhen Cui ◽  
...  
Keyword(s):  
Dna Replication ◽  
Prediction Models ◽  
Homo Sapiens ◽  
Computational Prediction ◽  
Specific Model ◽  
Gradient Boosting ◽  
Replication Process ◽  
Extreme Gradient Boosting ◽  
Feature Encoding ◽  
Process Detection

Abstract Origins of replication sites (ORIs), which refers to the initiative locations of genomic DNA replication, play essential roles in DNA replication process. Detection of ORIs’ distribution in genome scale is one of key steps to in-depth understanding their regulation mechanisms. In this study, we presented a novel machine learning-based approach called Stack-ORI encompassing 10 cell-specific prediction models for identifying ORIs from four different eukaryotic species (Homo sapiens, Mus musculus, Drosophila melanogaster and Arabidopsis thaliana). For each cell-specific model, we employed 12 feature encoding schemes that cover nucleic acid composition, position-specific and physicochemical properties information. The optimal feature set was identified from each encoding individually and developed their respective baseline models using the eXtreme Gradient Boosting (XGBoost) classifier. Subsequently, the predicted scores of 12 baseline models are integrated as a novel feature vector to train XGBoost and develop the final model. Extensive experimental results show that Stack-ORI achieves significantly better performance as compared with their baseline models on both training and independent datasets. Interestingly, Stack-ORI consistently outperforms existing predictor in all cell-specific models, not only on training but also on independent test. Moreover, our novel approach provides necessary interpretations that help understanding model success by leveraging the powerful SHapley Additive exPlanation algorithm, thus underlining the most important feature encoding schemes significant for predicting cell-specific ORIs.

Structure and function of the GINS complex, a key component of the eukaryotic replisome

2010 ◽  
Vol 425 (3) ◽  
pp. 489-500 ◽  
Author(s):  
Stuart A. MacNeill
Keyword(s):  
Replication Fork ◽  
Biochemical Analysis ◽  
Current Knowledge ◽  
Chromosomal Dna ◽  
Minichromosome Maintenance ◽  
Replication Process ◽  
Replicative Helicase ◽  
Cellular Life ◽  
Mcm Helicase ◽  
And Function

High-fidelity chromosomal DNA replication is fundamental to all forms of cellular life and requires the complex interplay of a wide variety of essential and non-essential protein factors in a spatially and temporally co-ordinated manner. In eukaryotes, the GINS complex (from the Japanese go-ichi-ni-san meaning 5-1-2-3, after the four related subunits of the complex Sld5, Psf1, Psf2 and Psf3) was recently identified as a novel factor essential for both the initiation and elongation stages of the replication process. Biochemical analysis has placed GINS at the heart of the eukaryotic replication apparatus as a component of the CMG [Cdc45–MCM (minichromosome maintenance) helicase–GINS] complex that most likely serves as the replicative helicase, unwinding duplex DNA ahead of the moving replication fork. GINS homologues are found in the archaea and have been shown to interact directly with the MCM helicase and with primase, suggesting a central role for the complex in archaeal chromosome replication also. The present review summarizes current knowledge of the structure, function and evolution of the GINS complex in eukaryotes and archaea, discusses possible functions of the GINS complex and highlights recent results that point to possible regulation of GINS function in response to DNA damage.

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