DNA Polymerases

The following sections are included:

• Preface

• Contents

The following sections are included:

• Discovering DNA: A First Step Towards Understanding the Basis of Life
  • Nuclein
  • Nucleic Acid
  • Nucleic Acids Are Composed of Nucleotides
  • DNA Is the Genetic Material
  • Structure of DNA: The Watson–Crick DNA Double Helix and Mechanism of DNA Replication

• Imaging an Enzyme that Assembles the Nucleotides into DNA
  • DNA Polymerase Activity in Extracts of Escherichia coli
  • Escherichia coli DNA Polymerase Can Synthesize DNA with Genetic Activity: Creating Life in the Test Tube
  • Bacteria Contain Many DNA Polymerases
  • How Is a New DNA Chain Started? Discontinuous DNA Synthesis and the Need for an RNA Primer
  • RNA Priming as a Mechanism for Initiation: DNA Primase

• Late 1960s to Early 1970s: DNA Replication Shows Its Complexity
  • DNA Structure Is Much More Complex, Rich of Conformational Flexibility and thus Full of Functional Potentialities than the One Proposed by Watson and Crick
  • DNA Binding Proteins, DNA Helicases, DNA Topoisomerases

• Concluding Remarks, Parts 1.1–1.3

• Multiple DNA Polymerases in Eukaryotic Cells: DNA Polymerases α, β and γ as the First Ones
  • DNA Polymerase α
  • DNA Polymerase β
  • Lack of Relationship Between High- and Low-Molecular Weight DNA Polymerases
  • 1975: First Nomenclature System for Eukaryotic DNA Polymerases
  • DNA Polymerase γ

• Early Attempts to Ascribe an in vivo Function to DNA Polymerases α, β and γ
  • Positive Correlation of DNA Polymerase α with Cellular DNA Replication and Development
  • DNA Polymerase γ Is the Mitochondrial DNA Polymerase and Replicates Mitochondrial DNA
  • Further Evidence for a Major Involvement of DNA Polymerase α in DNA Replication and of DNA Polymerase β in DNA Repair

• DNA Polymerases δ and ε

• 1985: Polymerase Chain Reaction (PCR), a Concept with Tremendous Practical Applications

• Yeast DNA Polymerases
  • Revised Nomenclature for Eukaryotic DNA Polymerases

• Plant Cell DNA Polymerases

• Virus-Induced DNA Polymerases
  • Herpes Virus DNA Polymerase
  • Vaccinia Virus DNA Polymerase
  • DNA Polymerase Activity in Hepatitis B Particle
  • Retroviruses Reverse Transcriptase

• 1999–2000: Nucleotide Sequence Analysis of Eukaryotic Organisms Allowed the Identification of Many Novel Specialized DNA Polymerases
  • DNA Polymerase ζ, the Lesion Extender
  • DNA Polymerases λ and μ, Two Family X DNA Polymerases
  • The Complex Y Family of DNA Polymerases
  • Present Nomenclature for Eukaryotic DNA Polymerases

• Concluding Remarks, Parts 1.5–1.12

• References

The following sections are included:

• Synthesis and Maintenance of DNA in Nature Need DNA Polymerases

• The DNA Polymerase Reaction

• The Universal Structure of a DNA Polymerase Resembles a Human Right Hand

• The Seven DNA Polymerase Families and Their Functions: An Overview

• DNA Polymerase Holoenzymes

• DNA Polymerases, Ring-Like Clamps and Clamp Loaders

• DNA Polymerases, Alternative Clamps and Clamp Loaders

• Replicative DNA Polymerases Interacting with Other Proteins

• DNA Polymerases and the Single-Stranded DNA Binding Protein Replication Protein A

• Chapter Summary

• References

The following sections are included:

• Escherichia coli
  • Family A: DNA Polymerase I
  • Family B: DNA Polymerase II
  • Family C: DNA Polymerase III Holoenzyme
  • Family Y: DNA Polymerases IV and V

• Bacillus subtilis
  • Family A: DNA Polymerase I
  • Family C: DNA Polymerase C and DnaE
  • Family X: DNA Polymerase X
  • Family Y: DNA Polymerases Y1 and Y2

• Other Bacteria
  • Mycobacteria
  • Deinococcus radiodurans

• Archaea
  • Family B: DNA Polymerase B
  • Family D: DNA Polymerase D
  • Family Y: DNA Polymerases Dbh and Dpo4

• Chapter Summary

• References

The following sections are included:

• The High Number of Specialized Pathways in Eukaryotic Cells Requires a Plethora of Specialized DNA Synthesizing Enzymes

• Eukaryotic DNA Polymerase Structure: The "Right Hand" of the Cell
  • Common Features
  • Specific Features of the Different Families

• Eukaryotic DNA Polymerases Accessory Subunits

• Eukaryotic DNA Polymerase Fidelity: Structural and Functional Aspects

• Biochemical and Functional Properties of the Different Eukaryotic DNA Polymerases
  • Family A DNA Polymerases
  • Family B DNA Polymerases
  • Family X DNA Polymerases
  • Family Y DNA Polymerases

• Interaction with Auxiliary Factors

• Eukaryotic DNA Polymerases Are Tightly Regulated in the Cell Cycle

• Chapter Summary

• References

The following sections are included:

• Fifteen DNA Polymerases: Share of Workload and Redundancies

• DNA Replication in Living Organisms Requires Three DNA Polymerase Molecules at the Replication Fork
  • Prokaryotes
    • Bacteriophage T7: The simplest but best known replisome
    • The Escherichia coli replisome
  • Eukaryotes
  • Proofreader versus Non-proofreader DNA Polymerases

• Different DNA Repair Pathways Have Their Own DNA Polymerases, But Can also Borrow Them from the Replication Machinery

• Translesion DNA Synthesis in Eukaryotes Generally Requires Two DNA Polymerases: An Inserter and an Extender

• Expression of DNA Polymerases

• DNA Polymerases Switch between Different DNA Transactions
  • Prokaryotes
  • Eukaryotes
    • Posttranslational modifications of PCNA
    • DNA pol switches due to PCNA ubiquitination
    • Other ways to regulate DNA polymerases

• Functions of DNA Polymerases in Checkpoint Control

• Chapter Summary

• References

The following sections are included:

• Bacteriophage T4 DNA Polymerase

• Bacteriophage T7 DNA Polymerase

• HSV-1 DNA Polymerase

• Protein Primed DNA Replication: Adenoviruses and Bacteriophage ϕ29
  • Adenovirus DNA Polymerase
  • Bacteriophage ϕ29 DNA Polymerase

• African Swine Virus DNA Polymerase

• RNA-Dependent DNA Synthesis: Reverse Transcriptases
  • HIV-1 Reverse Transcriptase
    • The retro-transcription reaction
    • Structural features of HIV-1 reverse transcriptase
    • Enzymatic features of HIV-1 reverse transcriptase
    • The RNase H activity of HIV-1 reverse transcriptase
  • Other Retroviral Reverse Transcriptases
    • HIV-2 reverse transcriptase
    • Murine Leukemia Virus (MLV) reverse transcriptase
    • Equine Infectious Anemia Virus (EIAV) reverse transcriptase
    • Feline Immunodeficiency Virus (FIV) reverse transcriptase
    • Mouse Mammary Tumor Virus (MMTV) reverse transcriptase
  • Reverse Transcriptase Activity of Mobile Genetic Elements: The Retrotransposons
    • Saccharomyces cerevisiae Ty reverse transcriptase
    • Schizosaccharomyces pombe Tf1 reverse transcriptase
    • Bombyx mori R2 reverse transcriptase
  • Hepadnavirus Reverse Transcriptase

• Chapter Summary

• References

The following sections are included:

• Why Design Enzymes with Novel Properties?

• DNA Polymerases Have a Tight Active Site to Which the Substrates Fit

• Methods to Evolve DNA Polymerases with Novel Properties
  • Detection and Characterization of DNA Polymerases and Mutants Thereof by Functional Complementation in Escherichia coli
  • DNA Polymerase Evolution by Random Point Mutagenesis
  • DNA Polymerase Evolution by Compartmentalized Self-Replication (CSR)
  • DNA Polymerase Evolution by Phage Display
  • DNA Polymerase Evolution by Oligonucleotide Addressed Enzyme Assay (OAEA)

• Applications of DNA Polymerases with Novel Properties

• DNA Polymerases with Novel Properties
  • Increased Fidelity
  • Decreased Fidelity
  • Amplification of Damaged and Ancient DNA
  • A DNA Polymerase Becomes an RNA Polymerase
  • Evolving the dNTP Substrates and Expansion of the Genetic Code

• Chapter Summary

• References

The following sections are included:

• Introduction

• DNA Polymerases and Genetic Stability

• DNA Polymerases and Resistance to Chemotherapy

• DNA Polymerase γ and Human Diseases

• Chapter Summary

• References

The following sections are included:

• DNA Polymerases Are Important Chemotherapeutic Targets

• Strategies and Problems for the Design of Inhibitors of DNA Polymerases
  • Substrate Analogs
  • Non-substrate Analogs
  • Novel in silico Technologies for Designing Inhibitors of DNA Polymerases

• Inhibitors of Herpesvirus DNA Replication
  • Anti-Herpetic Nucleoside Analogs Require Activation by the Viral Thymidine Kinase (TK)
  • Nucleoside Analogs Modified in the Base Ring
  • Nucleoside Analogs Modified in the Sugar Moiety
    • Arabinonucleosides
    • Acyclic nucleoside analogs
    • Carbocyclic nucleoside analogs
    • Phosphonate nucleoside analogs
  • Active-Site Directed Non-nucleoside Inhibitors of Herpesvirus DNA Polymerases

• The Lack of Enantioselectivity of Viral and Human Enzymes and the L-Enantiomers of Nucleosides: The Dawn of a New Generation of Antiviral Drugs
  • Herpesvirus Thymidine Kinase Has Low Enantioselectivity
  • The Discovery of a Relaxed Enantioselectivity of Human and Viral DNA Polymerases
  • Lack of Enantiospecificity of Human 2'-Deoxycytidine Kinase: Relevance for the Activation of L-Deoxycytidine Analogs

• Inhibitors of HIV-1 Reverse Transcriptase
  • Nucleoside Reverse Transcriptase Inhibitors
    • Intracellular anabolism of nucleoside reverse transcriptase inhibitors
    • Catabolism of nucleoside reverse transcriptase inhibitors
  • Non-nucleoside Reverse Transcriptase Inhibitors
    • Metabolism of non-nucleoside reverse transcriptase inhibitors
  • Combined Toxicities of Reverse Transcriptase Inhibitors
  • Molecular Interactions of HIV-1 Reverse Transcriptase with Nucleoside- and Non-nucleoside Inhibitors: The Problem of Drug Resistance
    • NRTIs drug resistance
    • NNRTIs drug resistance

• Inhibitors of Hepatitis B DNA Polymerase

• Chapter Summary

• References