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UV Light DNA Damage and Repair Mechanisms

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UV Light DNA Damage and Repair Mechanisms

This guide explains how ultraviolet (UV) light damages DNA at the molecular level and describes the primary repair mechanisms human cells use to fix that damage. You’ll learn the exact types of lesions UV causes, the enzymes involved in repair, and what happens when repair fails. No specialized equipment is needed—just a basic understanding of cell biology.

What You’ll Need

  • A basic biology textbook or reliable online resource for reference
  • Familiarity with terms like nucleotide, base pair, and enzyme
  • Optional: a notebook to sketch the repair pathways

Step-by-Step

  1. Understand the energy of UV light. UV light, especially UV-B (280–315 nm) and UV-C (100–280 nm), carries enough energy to be absorbed by DNA molecules. This absorption excites electrons in the DNA bases, leading to chemical changes.
  2. Identify the primary damage: cyclobutane pyrimidine dimers (CPDs). When two adjacent pyrimidine bases (thymine or cytosine) on the same DNA strand absorb UV, their double bonds can break and form a ring structure called a cyclobutane ring. This links the two bases together, distorting the DNA helix.
  3. Recognize the secondary damage: 6-4 photoproducts. UV can also cause a bond between the carbon-6 of one pyrimidine and the carbon-4 of an adjacent pyrimidine, creating a 6-4 photoproduct. This lesion is less common but more distorting to the DNA structure.
  4. Understand how these lesions block replication and transcription. The distorted helix prevents DNA polymerase (the enzyme that copies DNA) and RNA polymerase (the enzyme that reads genes) from moving past the damage. This can lead to mutations or cell death if not repaired.
  5. Learn the first repair mechanism: direct repair (photoreactivation). In humans, this pathway is not active (we lack the enzyme photolyase). However, it’s important to know that some organisms (like bacteria and plants) use photolyase to split the cyclobutane ring using visible light. Humans do not do this.
  6. Focus on the main human repair pathway: nucleotide excision repair (NER). This is the primary mechanism for removing bulky DNA lesions like CPDs and 6-4 photoproducts. It works in two sub-pathways: global genomic NER (GG-NER) and transcription-coupled NER (TC-NER).
  7. Step through GG-NER. In GG-NER, a protein complex (including XPC and DDB2) scans the genome for helix distortions. Once a lesion is found, the complex recruits other proteins (XPA, RPA, TFIIH) to verify the damage and unwind the DNA around it.
  8. Excise the damaged strand. Two endonucleases (XPG and ERCC1-XPF) cut the damaged DNA strand on both sides of the lesion, removing a short single-stranded DNA fragment (about 22–30 nucleotides long) that contains the damage.
  9. Fill the gap. DNA polymerase (either Pol δ or Pol ε) synthesizes new DNA to fill the gap, using the undamaged complementary strand as a template. Then DNA ligase seals the nick, restoring the original sequence.
  10. Understand TC-NER. When RNA polymerase stalls at a lesion during transcription, it recruits proteins (CSB and CSA) that displace the polymerase and recruit the same core NER machinery to excise and repair the damage. This ensures active genes are repaired preferentially.
  11. Know what happens if repair fails. If a CPD or 6-4 photoproduct is not repaired before replication, DNA polymerase may insert a random base opposite the lesion (translesion synthesis), leading to a mutation. Accumulated mutations can cause skin cancer.
  12. Consider additional defense: apoptosis. If the damage is too extensive, cells may trigger programmed cell death to prevent the propagation of mutated DNA.

Common Mistakes

  • Confusing NER with mismatch repair. NER removes bulky, helix-distorting lesions, while mismatch repair fixes small errors that occur during replication (like a wrong base pair). They use different proteins and mechanisms.
  • Thinking humans use photolyase. Humans do not have photolyase. We rely on NER. Direct repair is not a human pathway.
  • Assuming UV always causes mutations. UV damage is not a mutation itself; it’s a lesion. Mutations arise only if the lesion is bypassed by error-prone polymerases.
  • Overlooking the role of transcription-coupled repair. Some people forget that actively transcribed genes are repaired faster due to TC-NER.

Tips

  • Remember the acronym CPD: Cyclobutane Pyrimidine Dimer—think of the four-membered ring as a square.
  • Visualize the steps: recognition → unwinding → excision → synthesis → ligation. This makes the pathway easier to memorize.
  • Note that 6-4 photoproducts are more mutagenic per lesion because they cause more distortion and are repaired less efficiently.
  • Use mnemonics for the key proteins: XPA (verification), XPG (3′ cut), ERCC1-XPF (5′ cut).

Troubleshooting

  • If you’re confused about why UV causes cancer: The link is that unrepaired CPDs lead to C→T transitions (cytosine to thymine) during replication. These are the hallmark mutations in skin cancers.
  • If you can’t remember the difference between GG-NER and TC-NER: Think of GG-NER as a genome-wide patrol, while TC-NER is a targeted repair that follows RNA polymerase.
  • If you’re unsure about the size of the excised fragment: It’s roughly 22–30 nucleotides, but the exact number varies. Don’t memorize a single number; just know it’s a short patch.
  • If you wonder why UV-C is more damaging than UV-A: UV-C has higher energy and is absorbed more strongly by DNA, but it’s mostly filtered by the ozone layer. UV-A reaches the skin but causes damage indirectly through reactive oxygen species, which are repaired by base excision repair (BER), not NER.

Frequently Asked Questions

  • What is the most common UV-induced DNA lesion? The cyclobutane pyrimidine dimer (CPD) is the most frequent, accounting for about 75% of UV damage.
  • Can UV damage be repaired in the dark? Yes, nucleotide excision repair works in the dark and is the main repair pathway in humans. Photoreactivation (light-dependent) is not present in humans.
  • Why are people with xeroderma pigmentosum (XP) so sensitive to sunlight? XP is a genetic disorder caused by mutations in NER genes (like XPA, XPC, etc.). Without functional NER, UV lesions accumulate, leading to a very high risk of skin cancer.
  • Does sunscreen prevent DNA damage? Sunscreen absorbs or reflects UV, reducing the amount that reaches DNA. It does not repair existing damage, so it’s preventive, not curative.
  • What is the difference between a mutation and a DNA lesion? A lesion is a chemical alteration in the DNA (like a CPD). A mutation is a permanent change in the DNA sequence that is passed on to daughter cells. Lesions can lead to mutations if not repaired.
  • Can UV damage be repaired in any other way? Yes, base excision repair (BER) handles oxidative damage caused by UV-A (like 8-oxoguanine), but it does not repair CPDs or 6-4 photoproducts. Those require NER.

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