DNA is a double-stranded helix that stores genetic information. Its structure and topology are fundamental to its function in replication, transcription, and repair, and the molecule can adopt different conformations depending on sequence and environmental conditions.
Nucleotide Building Blocks
DNA is a polymer of deoxyribonucleotides, each consisting of three components. A nitrogenous base, either a purine (adenine or guanine) or a pyrimidine (cytosine or thymine), is attached to the 1-prime carbon of deoxyribose. A phosphate group is esterified to the 5-prime carbon. Nucleotides are linked by phosphodiester bonds between the 5-prime phosphate of one nucleotide and the 3-prime hydroxyl of the next, creating a sugar-phosphate backbone with directionality.
The Double Helix
The classic B-DNA structure, described by Watson and Crick in 1953, is a right-handed double helix with several key features. Two polynucleotide strands run antiparallel, with one oriented 5-prime to 3-prime and the other 3-prime to 5-prime. The sugar-phosphate backbones are on the outside, while the bases pair in the interior through hydrogen bonds. Adenine pairs with thymine through two hydrogen bonds, and guanine pairs with cytosine through three hydrogen bonds, making GC-rich sequences more stable. The helix has a diameter of about 2 nm, a rise of 0.34 nm per base pair, and completes one turn every 10.5 base pairs.
Alternative DNA Conformations
B-DNA is the most common form under physiological conditions, but DNA can adopt other conformations. A-DNA is a shorter, wider right-handed helix that forms under dehydrating conditions and is relevant to DNA-RNA hybrids. Z-DNA is a left-handed helix with a zigzag backbone that forms at alternating purine-pyrimidine sequences, particularly CG repeats. Z-DNA formation is favored by negative supercoiling and may have regulatory roles in transcription.
DNA Supercoiling
DNA in cells must be compacted to fit within the nucleus or cell. Circular DNA molecules, such as bacterial chromosomes and plasmids, become supercoiled when overwound or underwound. Negative supercoiling, where the DNA is underwound, is the natural state of most cellular DNA and facilitates strand separation needed for replication and transcription. Positive supercoiling occurs ahead of replication forks and must be relieved.
Topoisomerases are enzymes that manage DNA topology. Topoisomerase I creates a transient single-strand break to relieve torsional stress, changing the linking number by one. Topoisomerase II creates a double-strand break and passes another DNA segment through, changing the linking number by two. These enzymes are targets for anticancer drugs such as etoposide and camptothecin.
Chromatin Structure
Eukaryotic DNA is packaged into chromatin through association with histone proteins. The basic unit is the nucleosome, consisting of 147 base pairs of DNA wrapped around an octamer of core histones two each of H2A, H2B, H3, and H4. Linker histone H1 binds between nucleosomes, promoting higher-order folding. This packaging compacts DNA by approximately 10,000-fold and regulates access to genetic information.
DNA Denaturation and Renaturation
The two strands of DNA can be separated by heating or alkaline conditions that disrupt hydrogen bonds. Agarose gel electrophoresis uses these properties to separate DNA fragments by size. The melting temperature depends on GC content, with GC-rich DNA requiring higher temperatures for denaturation. DNA renaturation, also called annealing, occurs when cooling allows complementary strands to re-form the double helix. This process is the basis for hybridization techniques, including Southern blotting and DNA microarrays.
The Genetic Code
Genetic information is encoded in the linear sequence of bases in DNA. Three consecutive nucleotides form a codon, specifying one of twenty amino acids. The genetic code is degenerate, meaning most amino acids are specified by multiple codons, with the first two positions typically being most important. The code is nearly universal across all known organisms, strongly supporting a common evolutionary origin.
