DNA Structure

DNA is a polymer composed of repeating units called nucleotides. Each nucleotide consists of three components: a deoxyribose sugar, a phosphate group, and one of four nitrogenous bases. These bases are divided into purines (Adenine, Guanine) and pyrimidines (Cytosine, Thymine). The 'backbone' of the DNA strand is formed by alternating sugar and phosphate groups connected by 3'-5' phosphodiester bonds. The two strands are antiparallel, meaning they run in opposite directions (5' to 3' and 3' to 5'). Base pairing is specific: Adenine pairs with Thymine via two hydrogen bonds, while Cytosine pairs with Guanine via three hydrogen bonds. This complementary nature allows for high-fidelity replication and transcription. In eukaryotic cells, DNA is not free-floating; it is wrapped around histone proteins to form nucleosomes, which further condense into chromatin and eventually 46 chromosomes in the nucleus. Mitochondrial DNA remains circular and is inherited maternally. Disruptions to this structure, such as through ionizing radiation or chemical mutagens, can lead to mutations that cause diseases ranging from single-gene disorders to complex cancers.

The structure of DNA facilitates its primary functions: storage of information, replication, and transcription. The sequence of nitrogenous bases encodes the genetic instructions used in the development and functioning of all known living organisms. The central dogma of molecular biology describes the flow of genetic information from DNA to RNA (transcription) and from RNA to protein (translation). During the S-phase of the cell cycle, DNA polymerase synthesizes a new strand by reading the template strand. Because the C-G bond has three hydrogen bonds, it is more stable and requires more energy (higher melting temperature) to separate than A-T bonds. The major and minor grooves of the double helix provide binding sites for transcription factors and other regulatory proteins. Epigenetic modifications, such as DNA methylation (usually at CpG islands), can alter gene expression without changing the primary DNA sequence. Telomeres, repetitive TTAGGG sequences at the ends of chromosomes, protect against the loss of genetic material during replication and are maintained by the enzyme telomerase in specific cell types. Understanding these biochemical properties is essential for techniques such as Polymerase Chain Reaction (PCR), where heat is used to denature the DNA strands.

DNA structure is clinically relevant in oncology, hematology, and infectious diseases. Mutations in the DNA sequence—whether substitutions, deletions, or insertions—can result in dysfunctional proteins, leading to conditions like Sickle Cell Anemia or Cystic Fibrosis. Chromosomal aberrations, such as the Philadelphia chromosome (t9;22) in Chronic Myeloid Leukemia, result from structural breaks and reunions. Furthermore, the sensitivity of DNA to UV radiation explains the pathogenesis of skin cancers, where thymine dimers are formed. In the MLA context, clinicians must understand how molecular targeted therapies, such as PARP inhibitors in BRCA-mutated cancers, exploit DNA repair pathways. DNA structure also underpins forensic medicine and paternity testing through the analysis of Short Tandem Repeats (STRs).

Molecular investigations include: 1. PCR (Polymerase Chain Reaction) to amplify specific DNA sequences. 2. Sanger Sequencing for determining the exact order of bases in a gene. 3. Next-Generation Sequencing (NGS) for whole-genome or exome analysis. 4. Fluorescence In Situ Hybridisation (FISH) to detect structural abnormalities or gene mapping. 5. Microarray analysis to detect copy number variations (CNVs).

Not directly applicable to this basic-science topic; see related clinical topics.