Biology 1 - Lesson 15: DNA Structure and Replication
Deoxyribonucleic acid (DNA) is the hereditary material in all known cellular life forms. Its unique structure—a double helix made of two antiparallel strands—enables the stable storage of genetic information and accurate replication. Understanding DNA’s molecular characteristics and the replication process is fundamental to genetics, molecular biology, and biotechnology.
DNA Structure
James Watson and Francis Crick’s model of DNA (1953), built on data from Rosalind Franklin and Maurice Wilkins, showed that DNA is a double helix composed of nucleotide subunits. Each nucleotide consists of:
- Deoxyribose sugar (5-carbon sugar)
- Phosphate group
- Nitrogenous base (Adenine (A), Thymine (T), Guanine (G), Cytosine (C))
The sugar-phosphate backbones form the helix’s outer “rails,” while nitrogenous bases hydrogen bond in complementary pairs (A with T, G with C). Because the strands run in opposite 5′→3′ and 3′→5′ directions, the two DNA strands are described as antiparallel.
Double-Helix Stability and Base Pairing
Hydrogen bonds between complementary bases (A–T has two bonds; G–C has three) hold the strands together, and stacking interactions among adjacent base pairs further stabilize the helix. This specificity ensures fidelity in DNA replication and transcription:
- Purine bases (A, G) pair with pyrimidine bases (T, C).
- This consistent diameter (about 2 nm) keeps the double helix uniform.
Chromosome Organization
In prokaryotes, DNA is typically organized in a single circular chromosome found in the nucleoid region. Eukaryotes have multiple linear chromosomes in the nucleus, complexed with histone proteins into chromatin. During cell division, chromatin condenses into visible chromosomes. This packaging strategy helps manage large eukaryotic genomes while still granting regulated access for replication and gene expression.
Semiconservative Replication
DNA replication follows a semiconservative model, as demonstrated by the Meselson–Stahl experiment. Each new double helix retains one parental strand and one newly synthesized strand. This mechanism preserves the genetic information across cell divisions.
General Steps in DNA Replication
Though the details differ between prokaryotes and eukaryotes, the core steps of replication are similar:
- Initiation: Replication begins at specific origins of replication. In eukaryotes, multiple origins exist on each chromosome. Helicase unwinds the double helix, and single-strand binding proteins (SSBs) stabilize the unwound regions.
-
Elongation:
- Primase synthesizes a short RNA primer to provide a free 3′-OH group.
- DNA polymerase III (bacteria) or DNA polymerase δ/ε (eukaryotes) extends from the primer, adding nucleotides in the 5′→3′ direction.
- On the leading strand, synthesis is continuous, following the replication fork.
- On the lagging strand, short discontinuous segments (Okazaki fragments) are synthesized away from the fork and later joined by DNA ligase.
- Termination and Ligation: When replication forks meet or run off the chromosome ends, the RNA primers are removed (by RNase H in eukaryotes or DNA polymerase I in prokaryotes). DNA ligase seals the remaining nicks between Okazaki fragments, completing synthesis.
| Aspect | Prokaryotes | Eukaryotes |
|---|---|---|
| Chromosome Structure | Circular, single origin | Linear, multiple origins |
| Replication Rate | Faster (up to 1000 nt/s) | Slower (~50–100 nt/s) per fork |
| Polymerases | DNA pol I, II, III primarily | Multiple pols (α, δ, ε, etc.) |
| Telomeres | Not present (circular DNA) | Ends of linear chromosomes require telomerase |
Telomeres and Telomerase
In eukaryotes, the ends of linear chromosomes (telomeres) pose a replication challenge. DNA polymerases cannot completely replicate the 5′ ends, leading to progressive shortening with each cell division. Telomerase, an enzyme containing an RNA template, extends the 3′ end, compensating for this terminal sequence loss. Telomerase activity is critical in germ cells and many stem cells; in somatic cells, reduced telomerase contributes to cellular aging.
Proofreading and DNA Repair
DNA polymerases incorporate nucleotides with high fidelity and possess a 3′→5′ proofreading activity to remove mispaired bases. Additional repair mechanisms (e.g., mismatch repair, excision repair) correct remaining errors or damage from environmental sources (UV, chemicals). These systems collectively ensure genome stability and reduce mutation rates.
Conclusion
DNA’s double-helical structure and the semiconservative replication mechanism form the molecular basis of hereditary continuity in living organisms. The orchestration of replication—initiating at defined origins, proceeding bidirectionally, and resolving at chromosome termini—highlights the precision required for accurate genome duplication. Advances in understanding DNA replication have led to breakthroughs in medicine (e.g., cancer treatments targeting replication), biotechnology (PCR), and fundamental insights into how genetic information is perpetuated and altered across generations.
