Open Access Medical Books



Edited by David Stuart .

496 pages . 
DNA replication is a fundamental part of the life cycle of all organisms. Not surprisingly many aspects of this process display profound conservation across organisms in all domains of life. Successful duplication of the genetic material can decide the life or death of an organism. Hence, the integrity of the DNA replication process is paramount and any defects or errors can lead to a myriad of problems ranging from cell death and developmental failure to increased propensity for cancer.
The importance of accurately regulating the initiation and progression of DNA synthesis is reflected in the complexity involved in assembling the molecular machines that carry out chromosomal DNA synthesis. Chapters by Ishino & Ishino and Martinez-Antonio et al. discuss the process of DNA replication in bacteria and archaea and reveal aspects of the process that are conserved, and aspects that are unique when compared to eukaryotes.
The large size of eukaryotic chromosomes presents challenges to accomplishing accurate and timely DNA replication required for cell proliferation. The molecular machines that drive DNA unwinding and chromosomal DNA synthesis are assembled in a multi-step process that allows for many layers of potential regulation to ensure that DNA replication is initiated accurately and only when appropriate. Many of these mechanisms serve double duty to ensure that DNA replication is initiated only once in any given cell cycle. This is essential to ensure that all portions of the genome are replicated but that none are over-replicated which could lead to the formation of structures at risk for breakage or inappropriate recombination.
The assembly and activity of the DNA helicases and“replisome” that unwinds chromosomal DNA and drives DNA replication are reviewed and discussed in chapters by Stuart, Fisk et al., and Daniel, et al. The assembly of these fantastic DNA replication machines depends upon highly specific and exquisitely regulated protein-protein interactions achieved by specific interaction domains and a subset of these important interaction domains and mechanisms are reviewed in chapters by Matthews & Guarne and Zavec.
The Integrity of chromosomal DNA replication is a high priority for cells and there are many mechanisms devoted to ensuring that damage to chromosomes is limited during the duplication processes. The intra S-phase checkpoint and mechanisms that retain integrity of the replication forks in the face of conditions that lead to pausing or stalling of the replication process is discussed by Sabatinos & Forsburg who also present a model for the consequences of replication fork collapse during conditions when fork stalling or pausing occurs globally during the replication process. Cox & Mason describe the current state of understanding of the WRN helicase that functions in mammalian cells with emphasis on the effect of loss of function mutations in WRN that lead to Werners Syndrome, a disorder that recapitulates cellular aging.
Cellular DNA is not “naked” but is wrapped and folded into complex three-dimensional structures through its interaction with histone and other chromosomal proteins that comprise chromatin. The histone proteins are subject to an array of post-translational modifications that include acetylation, methylation, ubiquitination, and phosphorylation. The DNAprotein complex that is chromatin can exist in a range of structures varying in the degree of condensation and modification state of the proteins. Not surprisingly the state of the chromatin
has significant effects on the replication of the DNA, influencing the selection of start sites for DNA replication, the rate of fork progression and extent of fork pausing, as well as having effects on DNA repair and recombination. Chapters by Kubota et al., Aloui et al, Di Tomaso et al., Maya et al., and Galvani & Thiriet review aspects of the relationship of DNA replication to chromatin structure and epigenetic regulation.
Not all segments of chromosomal DNA are the same even within the same cell. Some regions of the chromosomes have unique characteristics required to carry out a particular function. The ends or telomeres of eukaryotic chromosomes are particularly interesting as they present a problem of how to fully replicate both strands without a loss of genetic information. The end replication problem and mechanisms that solve the problem are described in chapters by Grach and by Frydrychova and Mason.
This volume outlines and reviews the current state of knowledge on several key aspects of the DNA replication process. This is a critical process in both normal growth and development and in relation to a broad variety of pathological conditions including cancer. Understanding and defining the molecular mechanisms that drive and regulate DNA replication will offer insight into the fundamental process that allows cellular life and proliferation. Additionally, these insights will ultimately offer the hope of controlling diseases like cancer that deregulate DAN replication and cell proliferation.

David Stuart
Associate Professor
Department of Biochemistry
University of Alberta
Edmonton, Alberta


Section 1 of the textbook : Machines that Drive DNA Replication .

Chapter 1 Pulling the Trigger to Fire Origins of DNA Replication 3
David Stuart

Chapter 2 Replicative Helicases as the Central Organizing Motor Proteins 
in the Molecular Machines of the Elongating Eukaryotic Replication Fork 29
John C. Fisk, Michaelle D. Chojnacki and Thomas Melendy

Chapter 3 The MCM and RecQ Helicase Families: Ancient Roles in DNA 
Replication and Genomic Stability Lead to Distinct Roles in Human Disease 59
Dianne C. Daniel*, Ayuna V. Dagdanova and Edward M. Johnson

Chapter 4 DNA Replication in Archaea, the Third Domain of Life 91
Yoshizumi Ishino and Sonoko Ishino

Chapter 5 Proposal for a Minimal DNA Auto-Replicative System 127
Agustino Martinez-Antonio, Laura Espindola-Serna and Cesar Quiñones-Valles

Chapter 6 Extending the Interaction Repertoire of FHA and 
BRCT Domains 145
Lindsay A. Matthews and Alba Guarné

Chapter 7 Intrinsically Disoredered Proteins in Replication Process 169
Apolonija Bedina Zavec

Section 2 of the textbook : Mechanisms that Protect Chromosome Integrity During DNA Replication .

Chapter 8 Preserving the Replication Fork in Response to Nucleotide 
Starvation: Evading the Replication Fork Collapse Point 193
Sarah A. Sabatinos and Susan L. Forsburg

Chapter 9 The Role of WRN Helicase/Exonuclease in DNA 
Replication 219
Lynne S. Cox and Penelope A. Mason

Section 3 of the textbook : Replication of Organellar Chromosomes .

Chapter 10 Replicational Mutation Gradients, Dipole Moments, Nearest 
Neighbour Effects and DNA Polymerase Gamma Fidelity in Human Mitochondrial Genomes 257
Hervé Seligmann

Chapter 11 The Plant and Protist Organellar DNA Replication Enzyme POP 
Showing Up in Place of DNA Polymerase Gamma May Be a Suitable Antiprotozoal Drug Target 287
Takashi Moriyama and Naoki Sato

Section 4 of the textbook : Chromatin and Epigenetic Influences on DNA Replication .

Chapter 12 Roles of Methylation and Sequestration in the Mechanisms of 
DNA Replication in some Members of the Enterobacteriaceae Family 315
Amine Aloui, Alya El May, Saloua Kouass Sahbani and Ahmed Landoulsi

Chapter 13 The Mechanisms of Epigenetic Modifications During DNA 
Replication 333
Takeo Kubota, Kunio Miyake and Takae Hirasawa

Chapter 14 Chromatin Damage Patterns Shift According to Eu/ 
Heterochromatin Replication 351
María Vittoria Di Tomaso, Pablo Liddle, Laura Lafon-Hughes, Ana Laura Reyes-Ábalos and Gustavo Folle

Chapter 15 A Histone Cycle 377
Douglas Maya, Macarena Morillo-Huesca, Lidia Delgado Ramos, Sebastián Chávez and Mari-Cruz Muñoz-Centeno

Chapter 16 Replicating – DNA in the Refractory Chromatin 
Environment 403
Angélique Galvani and Christophe Thiriet

Section 5 of the textbook : Telomeres .

Chapter 17 Telomeres: Their Structure and Maintenance 423
Radmila Capkova Frydrychova and James M. Mason

Chapter 18 Telomere Shortening Mechanisms 445
Andrey Grach .

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Published by: Unknown - Wednesday, February 20, 2013


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