Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder. Patients with XP exhibit a cellular hypersensitivity to ultraviolet (UV) radiation, a high incidence of skin cancer and premature aging. Based on these clinical characteristics, what is the most likely cause for this disease?

Question

A.  defects in DNA repair
B.  defects in DNA replication
C.  lack of telomerase activity
D.  shortened telomeres

Clarify Question
· What is the key concept addressed by the question?
  · What type of thinking is required?
  · What key words does the question contain?

  Gather Content
· What do you already know about DNA replication and repair?

  Consider Possibilities
· What other information is related to the question? Which information is most useful?

  Choose Answer · Given what you now know, what information and/or problem solving approach is most likely to produce the correct answer?

  Reflect on Process
  · Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?
 

Answer 1

A.  defects in DNA repair

Clarify Question
· What is the key concept addressed by the question?
    o This question addresses DNA replication and repair.
  · What type of thinking is required?
    o This answer requires you to weigh and judge evidence – to Evaluate – and choose the best of the possible answers.
  · What key words does the question contain?
    o Xeroderma pigmentosum is a genetic disease. For this question, you simply need to understand its symptoms as described: sensitivity to UV, skin cancer, and aging.

  Gather Content
· What do you already know about DNA replication and repair?
    o DNA replication is the process that makes more DNA before cell division.
    o Along with replication, the enzyme telomerase adds telomeres to the ends of the DNA to protect them.
    o DNA repair is the process of recognizing and fixing damage to the DNA.
    o The damage can come from chemicals or from the UV radiation in sunlight.

  Consider Possibilities
· What other information is related to the question? Which information is most useful?
    o We are told that XP patients have three types of symptoms: sensitivity to UV, skin cancer, and premature aging. What ties together these three things?
    o You might consider a connection relating to telomeres. After all, an increase in telomerase activity is seen in cancer cells, and telomerase is thought to counteract aging.
    o But, the main problem from UV light is that it damages DNA by creating thymine dimers, not damaging telomeres. So that doesn’t fit.

  Choose Answer · Given what you now know, what information and/or problem solving approach is most likely to produce the correct answer?
    o What does it mean exactly to be hypersensitive to UV light? It means that UV is even more damaging than usual.
    o First consider what UV does to a healthy individual. The UV causes damage to the structure of DNA, which is recognized and repaired by enzymes.
    o If the DNA damage is not repaired, cancer can develop. DNA damage also contributes to aging, and DNA repair can slow the effects of aging.
    o So imagine an individual with a nonfunctional DNA repair process, due to a missing enzyme. UV-induced DNA damage would go unrepaired, leading to a high rate of skin cancer and increased effects of aging. This describes Xeroderma pigmentosum.

  Reflect on Process
  · Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?
    o This question required you to weigh and judge evidence – to Evaluate – and choose the best of the possible answers.
    o Did you recognize that sensitivity to UV, skin cancer, and aging all related to DNA repair?
    o Xeroderma pigmentosum cannot be cured. But with special precautions, individuals can live into middle age. What precautions would you recommend to an XP patient?