DNA
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Foundations
Foundations
1. DNA as the primary hereditary macromolecule
Deoxyribonucleic acid (DNA) is a nucleic-acid polymer that stores genetic instructions used in development, growth, functioning, and reproduction of all known organisms and many viruses. Together with RNA, it forms the class of nucleic acids, one of the four major life macromolecules. DNA’s information content is carried in the order of its bases and can be copied and transmitted between cells and generations.
Molecular structure
Molecular structure
2. Nucleotides, backbone chemistry, and base categories
DNA strands are polynucleotides built from nucleotide monomers, each containing a deoxyribose sugar, a phosphate group, and one base (A, T, C, or G). Nucleotides link via covalent phosphodiester bonds to form an alternating sugar–phosphate backbone. Bases fall into purines (A,G; double-ring) and pyrimidines (C,T; single-ring), and their chemistry underlies pairing specificity.
Molecular structure
3. Double helix, complementarity, and antiparallel directionality
Most DNA exists as double-stranded DNA (dsDNA) where two strands coil into a double helix and run antiparallel, meaning one strand is oriented 5′→3′ while the other is 3′→5′. Each strand has a 5′ end (terminal phosphate) and a 3′ end (terminal hydroxyl), giving polarity. Complementary base pairing (A–T, C–G) means each strand encodes the same information, enabling templated copying.
Biophysical properties
Biophysical properties
4. Stabilizing forces: hydrogen bonding and base stacking
The double helix is stabilized by hydrogen bonds between complementary bases and by intrastrand base-stacking interactions among aromatic nucleobases. A–T pairs form two hydrogen bonds, while G–C pairs form three, and G/C stacking is often especially stabilizing. Because stacking and pairing are noncovalent, strands can separate (“melt”) under conditions like high temperature, low salt, or high pH, and reanneal when conditions normalize.
Biophysical properties
5. Canonical dimensions and physical measurements of DNA
Typical B-form DNA has a helical pitch of 34 Å (3.4 nm) and a radius near 10 Å (1.0 nm). Reported widths can vary by solution conditions, with measurements such as 22–26 Å (2.2–2.6 nm) cited in different buffers. One nucleotide unit is about 3.3 Å (0.33 nm) in length along the helix axis, and the buoyant density of most DNA is about 1.7 g/cm³, reflecting composition and packing.
Protein–DNA interactions
Protein–DNA interactions
6. Grooves and sequence readout by proteins
The helix creates major and minor grooves that differ in size because strands are offset. In B-DNA the major groove is ~22 Å (2.2 nm) wide and the minor groove is ~12 Å (1.2 nm). Base edges are more accessible in the major groove, so many sequence-specific DNA-binding proteins (e.g., transcription factors) “read” DNA by contacting functional groups exposed there. Groove geometry thus links structure to gene regulation.
Biophysical properties
Biophysical properties
7. Melting temperature (Tm) and determinants of duplex stability
Duplex stability depends on GC content, sequence context (stacking is sequence-specific), ionic strength, DNA concentration, and molecule length. A widely used metric is the melting temperature (Tm), the temperature at which 50% of dsDNA becomes single-stranded. Longer helices and higher GC content generally raise Tm, while AT-rich regions lower it; biologically, promoters that must open readily often contain AT-rich motifs (e.g., Pribnow/TATAAT).
Cellular organization
Cellular organization
8. Genome packaging in cells: chromosomes, chromatin, and nucleosomes
In eukaryotes, DNA is packaged into chromosomes and compacted with chromatin proteins such as histones. Histones form nucleosomes—disk-like cores around which DNA wraps in about two turns—creating an organized, compact structure that influences accessibility to transcription machinery. Prokaryotes store DNA in the cytoplasm, typically as circular chromosomes within a nucleoid region. Packaging helps fit DNA into cellular space and regulates which sequences are transcribed.
Core processes
Core processes
9. DNA replication, transcription, and translation as the information flow
Complementarity enables DNA replication: strands separate and each serves as a template for synthesis by DNA polymerases, which extend only in the 5′→3′ direction, requiring distinct mechanisms for leading and lagging strands. In transcription, DNA templates RNA (with uracil replacing thymine), and in translation, mRNA codons specify amino-acid sequences in proteins. This DNA→RNA→protein relationship is a core organizing principle in molecular biology.
Genomics data
Genomics data
10. Quantitative human genome facts (nuclear and mitochondrial)
Human nuclear DNA totals ~3.1–3.2 billion base pairs per haploid set (23 chromosomes); somatic cells are diploid with 46 chromosomes and ~6.3–6.4 Gbp, about 2 m of DNA and ~6–7 pg per cell. Mitochondrial DNA is a 16,569 bp circular genome present in hundreds to thousands of copies per cell. DNA stores, copies, and transmits genetic information.
Epigenetics & modification
Epigenetics & modification
11. Noncanonical bases and epigenetic regulation via methylation
DNA can contain modified (noncanonical) bases, notably 5-methylcytosine, recognized historically in 1925. In bacteria and phages, unusual bases can help evade restriction enzymes. In plants and animals, cytosine and adenine modifications contribute to epigenetic control of gene expression by altering chromatin state and transcriptional accessibility. Cytosine methylation is also implicated in X-chromosome inactivation; methylated cytosines can deaminate to thymine, increasing mutation susceptibility.
Damage & repair
Damage & repair
12. DNA damage, mutagens, and the scale of oxidative lesions
DNA is altered by mutagens such as UV light, X-rays, oxidants, and alkylating agents. UV can form thymine dimers, while oxidative stress can produce base modifications and double-strand breaks, which are among the hardest lesions to repair and can drive mutations and cancer. A quantitative claim in the text is that a typical human cell contains about 150,000 bases that have suffered oxidative damage; unrepaired damage can accumulate with age, linking DNA lesions to aging biology.
Topology & conformations
Topology & conformations
13. Supercoiling, topoisomerases, and torsional control
DNA can be over- or under-wound relative to its relaxed twist (about one turn per 10.4 bp). Positive supercoiling tightens winding and stabilizes pairing; negative supercoiling loosens winding and helps strand separation. Cells commonly maintain slight negative supercoiling using topoisomerases, which cut and reseal DNA to manage torsional stress generated during replication and transcription. This mechanical regulation is essential for genome stability and gene expression dynamics.
Topology & conformations
14. Alternative DNA conformations and specialized end structures
Beyond common B-DNA, DNA can adopt A-DNA (wider, right-handed; favored by dehydration and some DNA–RNA hybrids) and Z-DNA (left-handed; associated with certain sequences and base modifications like methylation). Linear chromosomes end in telomeres, often rich in TTAGGG repeats in humans, which protect ends and solve replication limits via telomerase. Telomeric guanine-rich tracts can form G-quadruplexes (stacked guanine tetrads) and T-loops/D-loops that further stabilize chromosome ends.