Structural organization of the hepatitis B virus minichromosome.

1. Quantitative Radiation Biology.- 1.1 Radiation in Society.- 1.2 Radiation Biology: the Interdisciplinary Discipline.- 1.3 The Importance of Cellular Biology.- 1.4 The Quantitative Analysis of Radiation Action: a Brief Historical Review.- 1.5 Desiderata for a Quantitative Theory of Radiation Biology.- 2. The DNA Molecule and Its Role in the Cell.- 2.1 Introduction.- 2.2 The Structure and Dimensions of the DNA Molecule.- 2.3 Base Sequences and the Genetic Code.- 2.4 DNA Replication.- 2.5 DNA in Chromosomes.- 2.6 The Diploid Cell, Mitosis and Meiosis.- 2.7 Radiation-Induced Damage to DNA.- 2.7.1 DNA Base Damage.- 2.7.2 DNA Single Strand Breaks.- 2.7.3 DNA Double Strand Breaks.- 3. The Molecular Model for Cell Survival Following Radiation.- 3.1 Historical Development.- 3.2 The Philosophical Framework of the Model.- 3.3 The Induction of DNA Double Strand Breaks by Radiation.- 3.3.1 The Induction of DNA Single Strand Breaks.- 3.3.2 The Induction of DNA Double Strand Breaks in One Radiation Event.- 3.3.3 The Induction of DNA Double Strand Breaks in Two Radiation Events.- 3.3.4 The Total Induction of DNA Double Strand Breaks.- 3.3.5 The Induction of DNA Double Strand Breaks with Repair.- 3.3.6 The Influence of Base Damage on the Production of Double Strand Breaks.- 3.4 The Relationship Between Cell Survival and DNA Double Strand Breaks.- 3.5 The Cell Survival Curve.- 3.5.1 Cell Survival as Criterium.- 3.5.2 Correction for Cell Multiplicity.- 3.5.3 The Shape of the Cell Survival Curve.- 3.5.4 The Analysis of Experimental Data.- 3.6 Variation in the Survival Curve Through the Cell Cycle.- 3.7 Asynchronous Cell Populations.- 3.8 The Experimental Correlation Between Cell Survival and DNA Double Strand Breaks.- 3.9 Summary.- 4. Chromosomal Aberrations.- 4.1 Introduction.- 4.2 The Nature and Yield of Chromosomal Aberrations.- 4.3 The Classical and Exchange Theories of Radiation- Induced Chromosomal Aberrations.- 4.3.1 The Classical Theory.- 4.3.2 The Exchange Theory.- 4.3.3 The Problem.- 4.4 The Molecular Theory of Radiation-Induced Chromosomal Aberrations.- 4.4.1 The Yield of Chromosomal Aberrations.- 4.4.2 The Formation of Chromosomal Aberrations by the Process of Telomere-Break Rejoining.- 4.4.2.1 A Possible Molecular Mechanism for Rejoining Between a Telomere and a Break and the Stabilization of a Broken End.- 4.4.3 The Formation of Chromosomal Aberrations by the Process of Recombinational Rejoining.- 4.4.3.1 Repetitive DNA.- 4.4.3.2 Palindromes.- 4.4.3.3 Incompleteness.- 4.4.4 The Experimental Evidence for Telomere-Break Rejoining.- 4.4.4.1 The Haplopappus Experiment.- 4.4.4.2 Other Radiation Experiments.- 4.4.4.3 Medical Cytology.- 4.4.5 The Experimental Evidence for the Process of Recip--rocal Recombination.- 4.4.6 Two Mechanisms for the Formation of Chromosomal Aberrations?.- 4.4.6.1 The Molecular Nature of the Telomere.- 4.4.6.2 The Role of Caffeine.- 4.5 Complex Chromosomal Rearrangements.- 4.6 Gene Transplantation.- 4.7 Summary.- 5. Somatic Mutations.- 5.1 Point and Chromosome Mutations.- 5.2 Some Molecular Mechanisms Which Could Give Rise to Mutations from DNA Double Strand Breaks.- 5.2.1 The Rejoining of Single Stranded Tails.- 5.2.2 Resnick's Model for Gene Conversion.- 5.2.3 Resnick's Model for Reciprocal Recombination.- 5.2.4 Rejoining Between a Telomere and a Single Stranded Tail.- 5.2.5 No Repair.- 5.2.6 The Repair Processes and Mutation Induction.- 5.3 Mutation Frequency Dose Relationships.- 5.3.1 The Induction of Mutations.- 5.3.2 The Suppression of Mutation Expression.- 5.3.3 The Influence of Cell Killing.- 5.4 The Analysis of Experimental Data.- 5.5 Two Mutations in the Same Cell Population.- 5.6 The Mutation Spectrum.- 5.7 Summary.- 6. Correlations.- 6.1 Introduction.- 6.2 The Survival-Survival Correlation.- 6.3 The Survival-Chromosomal Aberration Correlation.- 6.4 The Correlation Between Different Chromosomal Aberrations.- 6.5 The Correlation Between "Normal" Chromosomal Aberrations and "Complex" Chromosomal Aberrations.- 6.6 The Correlation Between Survival and Somatic Mutation.- 6.7 The Correlation Between Two Different Mutations Induced in the Same Cell Population.- 6.8 The Peak Incidence - an Implied Correlation.- 6.9 What Do the Correlations Mean?.- 7. Repair.- 7.1 Introduction.- 7.2 The Repair of DNA Single Strand Breaks and the Dose Rate Effect.- 7.2.1 Experimental Evidence on DNA Single Strand Break Repair.- 7.2.2 The Time Scale of the Three Dose Rate Regions.- 7.2.3 The Exponential Repair of DNA Single Strand Breaks and Its Effect on the Dose Response Relationships.- 7.2.4 Implications for the InS/D Versus D Analysis.- 7.2.5 Complicated Repair Rates.- 7.2.6 Practical Difficulties in the Determination of Dose-rate Effects.- 7.3 The Repair of DNA Single Strand Breaks and the Effect of Dose Fractionation.- 7.3.1 The Analysis of Repair Using Fractionation Studies.- 7.4 The Repair of DNA Double Strand Breaks and the Post-Irradiation Effect.- 7.4.1 The Quantitative Effect of DNA Double Strand Break Repair on Cell Survival.- 7.4.1.1 The Time Dependence of the Repair of DNA Double Strand Breaks.- 7.4.2 The Quantitative Effect of DNA Double Strand Break Repair on Chromosomal Aberration Yield.- 7.4.3 The Quantitative Effect of DNA Double Strand Break Repair on Mutation Frequency.- 7.4.4 Is the Efficiency for the Repair of DNA Double Strand Breaks Always Dose-independent?.- 7.5 The Difference Between Sub-lethal Damage Repair and Potentially Lethal Damage Repair.- 8. Radiation Quality.- 8.1 The Differing Shape of Dose-response Relationships.- 8.2 A Qualitative Assessment of the Dependence of the ?-Coefficient on Radiation Quality.- 8.3 A Qualitative Assessment of the Dependence of the ?-Coefficient on Radiation Quality.- 8.4 How Constant is the Value of RBEo?.- 8.4.1 The Variation of RBEo in the Cell Cycle.- 8.4.2 The Effect of Different Conditions in the Cell.- 8.4.3 Extremely High Values of RBEo.- 8.5 The Size of the Target.- 8.6 A Calculation of the Dependence of the a- and ss- Coefficients on Radiation Quality.- 8.6.1 The Track Model.- 8.6.2 A Calculation of the Induction of DNA Single and Double Strand Breaks.- 8.6.3 A Quantitative Assessment of the Dependence of Cell Survival on Radiation Quality.- 8.6.4 The Relation Between Physics, Chemistry, and Biology.- 8.7 Summary.- 9. Cancer.- 9.1 Introduction.- 9.2 Somatic Mutation and Cancer.- 9.2.1 Historical Development.- 9.2.2 The Modern Evidence Supporting the Somatic Mutation Theory.- 9.2.2.1 The Mutagen Screening Tests.- 9.2.2.2 The Typical Chromosomal Aberrations.- 9.2.2.3 The Repair-deficient Human Disorders.- 9.3 The Malignant Cell.- 9.4 Radiation-Induced Cell Transformation.- 9.4.1 The Diploid Carrier Cell.- 9.4.2 The Tetraploid Carrier Cell.- 9.4.3 The Diploid Non-Carrier Cell.- 9.5 Extrapolation to Animals and Man.- 9.5.1 Experimental Data for Animals.- 9.5.2 Radiation-induced Malignancy in Man.- 9.5.2.1 Sparsely Ionizing Radiation.- 9.5.2.2 Densely Ionizing Radiation.- 9.6 Conclusion.- 10. Genetic Effects.- 10.1 Introduction.- 10.2 The Induction of Dominant Lethal Mutations.- 10.3 Correlations Between Different Genetic End Points.- 10.3.1 The Correlation Between Dominant Lethality and the Yield of Chromosomal Aberrations.- 10.3.2 The Correlation Between Different Chromosomal Aberrations.- 10.3.3 The Correlation Between Dominant Visible Mutations and Specific Locus Mutations in the Mouse.- 10.3.4 The Correlation Between Dominant and Recessive Lethal Mutations.- 10.4 The Induction of Translocations in the Spermatogonia of the Mouse.- 10.4.1 The Spermatogonial Stem Cell Development.- 10.4.2 Acute Irradiation.- 10.4.3 The Effect of Dose Rate.- 10.4.4 Short-Term Fractionation.- 10.4.5 Twenty-Four-Hour Fractionation.- 10.4.6 Long-Term Fractionation.- 10.5 The Induction of Specific Locus Mutations in the Mouse.- 10.6 Conclusions.- 11. Synergistic Interaction.- 11.1 Introduction.- 11.2 Theoretical Development.- 11.3 Agent Toxicity.- 11.4 Agent Dosimetry.- 11.5 Experimental Examples of Synergism.- 11.5.1 The Interaction of Radiation with UV.- 11.5.2 The Interaction of Radiation with Halogenated Pyrimidine Analogues.- 11.5.3 The Interaction of Radiation with Nitrosourea Compounds.- 11.5.4 The Interaction of Radiation with Diamide.- 11.6 General Discussion.- 12. Implications.- 12.1 Radiological Protection.- 12.1.1 Sparsely Ionizing Radiation.- 12.1.2 Densely Ionizing Radiation.- 12.1.3 Cancer as a Recessive Genetic Character.- 12.1.4 Genetic Effects.- 12.1.5 The Effect of Environmental Mutagens.- 12.2 The Chemical Hazard.- 12.3 Radiation Therapy.- 12.3.1 Fractionation.- 12.3.1.1 ?-Type Sensitizer.- 12.3.1.2 ?-Type Sensitizer.- 12.3.1.3 Implications for the Choice of Sensitizer.- 12.4 Plant Mutation Breeding.- 12.5 Postscript.- References.- List of Abbreviations.

The Molecular Theory of Radiation Biology

Counting nucleosomes in living cells with a combination of fluorescence correlation spectroscopy and confocal imaging.

Chromatin assembly is required for the duplication of chromosomes ACF (ATP-utilizing chromatin assembly and remodeling factor) catalyzes the ATP-dependent assembly of periodic nucleosome arrays in vitro, and consists of Acf1 and the ISWI ATPase Acf1 and ISWI are also subunits of CHRAC (chromatin accessibility complex), whose biochemical activities are similar to those of ACF Here we investigate the in vivo function of the Acf1 subunit of ACF/CHRAC in Drosophila Although most Acf1 null animals die during the larval-pupal transition, Acf1 is not absolutely required for viability The loss of Acf1 results in a decrease in the periodicity of nucleosome arrays as well as a shorter nucleosomal repeat length in bulk chromatin in embryos Biochemical experiments with Acf1-deficient embryo extracts further indicate that ACF/CHRAC is a major chromatin assembly factor in Drosophila The phenotypes of flies lacking Acf1 suggest that ACF/CHRAC promotes the formation of repressive chromatin The acf1 gene is involved in the establishment and/or maintenance of transcriptional silencing in pericentric heterochromatin and in the chromatin-dependent repression by Polycomb group genes Moreover, cells in animals lacking Acf1 exhibit an acceleration of progression through S phase, which is consistent with a decrease in chromatin-mediated repression of DNA replication In addition, acf1 genetically interacts with nap1, which encodes the NAP-1 nucleosome assembly protein These findings collectively indicate that ACF/CHRAC functions in the assembly of periodic nucleosome arrays that contribute to the repression of genetic activity in the eukaryotic nucleus

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Acf1 confers unique activities to ACF/CHRAC and promotes the formation rather than disruption of chromatin in vivo

Variation in chromatin structure in two cell types from the same tissue: a short DNA repeat length in cerebral cortex neurons

Biochemical evidence is presented which confirms that the DNA repeat length in micrococcal nuclease (spleen endonuclease, nucleate 3'-oligonucleotidohydrolase, EC 3-1-4-7) digests of Chinese hamster ovary chromatin is shorter than that of rat liver chromatin [J.L. Compton, R. Hancock, P. Oudet, and P. Chambon (1976) Eur. J. Biochem., in press]. A survey of available cells has shown that the DNA repeat length of the chromatin of higher eukaryotes varies widely. A value of 196 base pairs was found for cells of all mature tissues, regardless of the source of the tissue, whereas smaller values were found for cells of actively dividing tissues and larger values were found for a genetically inactive cell. Although the DNA repeat length of the chromatin of cells in culture was usually shorter than 196 base pairs, there was no general correlation between the size of the chromatin DNA repeat length and the rate of cell division or the functional state of the cell in culture. Examination of extensive micrococcal nuclease digests suggests that the chromatin subunits of all of the higher eukaryotic cells we have studied contain a core with approximately 140 base pairs of DNA.

https://www.pnas.org/content/pnas/73/12/4382.full.pdf

J L Compton

Papers

Biochemical evidence of variability in the DNA repeat length in the chromatin of higher eukaryotes.