Preview
IB DP Biology — Unit D: Continuity and Change | SL | D1.1 DNA Replication and Repair
📋 What You Will Learn
- Identify the major sources of DNA damage and the types of lesions they produce in the double helix
- Explain the molecular mechanisms of nucleotide excision repair, base excision repair, and mismatch repair
- Analyse data from experiments investigating mutation rates and repair efficiency in different biological contexts
- Apply understanding of repair pathway failure to explain the link between DNA damage, mutation accumulation, and cancer
- Evaluate the significance of DNA repair fidelity for inheritance, evolution, and genome stability
🔍 Guiding Question How do cells detect and correct errors in DNA, and what are the consequences when these repair mechanisms fail?
🌍 Why This Matters Every time you step into sunlight, ultraviolet radiation is colliding with the DNA in your skin cells and fusing adjacent thymine bases together. Without a dedicated repair system scanning your genome for exactly this kind of damage, those fused bases would be misread at the next replication, and mutations would accumulate with every sunny afternoon. Xeroderma pigmentosum — a rare inherited condition in which nucleotide excision repair is non-functional — makes this invisible threat visible: affected individuals develop skin cancers at a rate thousands of times higher than the general population, simply because one repair pathway is missing.
The Problem the Cell Had to Solve
Here is the fundamental tension at the heart of this topic: DNA must be stable enough to preserve genetic information across generations, yet it is a molecule made of atoms — and atoms react. Every day, each human cell suffers an estimated 10,000 to 100,000 DNA lesions from chemical reactions, radiation, and replication errors. Left uncorrected, these lesions become permanent mutations. The cell's solution is a suite of damage recognition and repair pathways so sophisticated that the overall mutation rate per base pair per replication is kept below one in a billion.
Understanding these pathways is not just molecular detail — it is the story of how life maintains continuity across time. The theme of Continuity and Change runs directly through this topic: repair systems preserve continuity, while their occasional failure generates the variation that drives change.
📖 Key Definition — DNA Lesion A DNA lesion is any structural alteration to the DNA molecule that disrupts normal base-pairing, replication, or transcription. Lesions include modified bases, strand breaks, and covalent crosslinks between bases.
Sources of DNA Damage
Before a cell can repair damage, it must first understand where damage comes from. The sources are both external and internal — the genome is under attack from the environment and from the cell's own chemistry simultaneously.
Endogenous (Internal) Sources
The most frequent source of DNA damage is the cell's own metabolic activity. Reactive oxygen species (ROS) — byproducts of aerobic respiration in mitochondria — attack guanine bases, converting them to 8-oxoguanine, which mispairs with adenine instead of cytosine. Hydrolysis reactions spontaneously remove bases from the sugar-phosphate backbone, creating abasic (apurinic/apyrimidinic) sites at a rate of approximately 10,000 per cell per day. Spontaneous deamination converts cytosine to uracil, which would be read as thymine at the next replication.
Replication errors also contribute: DNA polymerase occasionally inserts the wrong nucleotide. Although the polymerase has a 3'→5' proofreading exonuclease activity that catches most errors immediately, roughly one