DNA Types and Structure

Structure of DNA

The hereditary material DNA is a double-stranded nucleotide polymer: 

• Organization of DNA:
  • In eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic cells, DNA can be found in the cell nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles and the mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles:
    • The chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics is the organizing unit of DNA.
    • In humans: 46 homologous chromosomes Homologous chromosomes Basic Terms of Genetics (23 pairs)
    • Coding information contained within segments of chromosomes called genes
  • In prokaryotes, DNA is in cytoplasm as a plasmid or chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics.
• Structure of DNA:
  • 2 antiparallel strands (opposite polarity) forming a double-helix: 10.5 base pairs per turn of helix
  • Negatively charged sugar-phosphate backbone
  • Complementary strands held together by:
    • Hydrogen bonds
    • Van der Waals forces
    • Hydrophobic interactions between base pairs
  • Free 5’–3’ carbon ends on each strand
  • Described by James Watson and Francis Crick (awarded Nobel Prize in Physiology or Medicine in 1962)
  • Rosalind Franklin’s work with X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests crystallography was essential to the discovery of DNA’s structure.
• Nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids are the monomers that make up DNA:
  • Nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids in DNA (deoxyribonucleotides):
    • Deoxyadenosine triphosphate (dATP)
    • Deoxyguanosine triphosphate (dGTP)
    • Deoxycytidine triphosphate (dCTP)
    • Deoxythymidine triphosphate (dTTP)
  • Nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids are linked through 3’–5’ phosphodiester bonds:
    • Energy for synthesis Synthesis Polymerase Chain Reaction (PCR) comes from releasing 2 phosphates (dATP → deoxyadenosine monophosphate (dAMP)).
    • Synthesis Synthesis Polymerase Chain Reaction (PCR) occurs in 5’–3” direction.
    • Purines Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. Nucleic Acids pair with pyrimidines Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine; thymine; and uracil) and form the basic structure of the barbiturates. Nucleic Acids:
      • Adenine Adenine A purine base and a fundamental unit of adenine nucleotides. Nucleic Acids (purine) ↔ thymine Thymine One of four constituent bases of DNA. Nucleic Acids (pyrimidine)
      • Guanine Guanine Nucleic Acids (purine) ↔ cytosine Cytosine A pyrimidine base that is a fundamental unit of nucleic acids. Nucleic Acids (pyrimidine)

Organization and Packing of DNA in the Cell Nucleus

• In the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles, DNA is condensed into chromosomes by nucleic proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis.
• Order of DNA condensation: double-stranded DNA (dsDNA) → nucleosomes → solenoid strand → chromatin loops → chromosomes
  • Negatively charged dsDNA is wrapped around positively charged histone octamers to form nucleosomes.
  • Histones undergo modifications, which affect access to DNA and thus transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription (TX):
    • Acetylation Acetylation Formation of an acetyl derivative. Chloramphenicol (increases TX)
    • Methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids (increases or decreases TX, epigenetics → heritable)
    • Phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing (increases or decreases TX)
    • Ubiquitylation Ubiquitylation The act of ligating ubiquitins to proteins to form ubiquitin-protein ligase complexes to label proteins for transport to the proteasome endopeptidase complex where proteolysis occurs. Post-translational Protein Processing
    • ADP-ribosylation ADP-ribosylation Post-translational modification of proteins with adenosine diphosphate ribose. Diphtheria
• Forms of chromatin:
  • Euchromatin (decondensed form): transcriptionally active
  • Heterochromatin (condensed form): transcriptionally inactive

Mitochondrial DNA

• Mitochondrial DNA (mtDNA) represents 1% of cellular DNA.
• Only inherited from the mother (non-Mendelian inheritance)
• Characteristics of human mtDNA:
  • Circular, double-stranded, composed of heavy (H) and light (L) strands
  • Contains 16,569 base pairs
  • Encodes ribosomal RNAs, tRNAs, and protein subunits necessary for oxidative phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing (ATP production)
  • High mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations rate (5–10 times that of nuclear DNA Nuclear DNA Mitochondrial Myopathies)
• Presence of mtDNA led to theory of endosymbiosis:
  • Mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles 
  • Once free-living prokaryotic Prokaryotic Prokaryotes are unicellular organisms that include 2 of the 3 domains of life: bacteria and archaea. Prokaryotic cells consist of a single cytoplasm-filled compartment enclosed by a cell membrane and cell wall. Cell Types: Eukaryotic versus Prokaryotic microbes
  • Engulfed by host cell and became organelles Organelles A cell is a complex unit that performs several complex functions. An organelle is a specialized subunit within a cell that fulfills a specific role or function. Organelles are enclosed within their own lipid bilayers or are unbound by membranes. The Cell: Organelles
  • Circular DNA
  • Replication by binary fission Binary fission Cell Types: Eukaryotic versus Prokaryotic

Clinical Relevance

• Mitochondrial myopathies: caused by mitochondrial diseases where “ragged red” muscle fibers are observed by biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. The myopathy Myopathy Dermatomyositis resembles the accumulation of glycogen and neutral lipids Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids, which may be correlated with an increased reactivity for succinate dehydrogenase Succinate dehydrogenase A flavoprotein containing oxidoreductase that catalyzes the dehydrogenation of succinate to fumarate. In most eukaryotic organisms this enzyme is a component of mitochondrial electron transport complex II. Citric Acid Cycle and a decreased reactivity for cytochrome c oxidase Oxidase Neisseria. Both mitochondrial and nuclear DNA Nuclear DNA Mitochondrial Myopathies mutations underlie mitochondrial myopathy Myopathy Dermatomyositis.
• Genetic mutations Genetic Mutations Carcinogenesis: errors in the DNA that sometimes cause abnormal protein function. There are various types of mutations categories and subcategories including chromosomal, point, frameshift, and expansion mutations. Point mutations include missense, nonsense, single, and silent mutations.