Now that the sunny weather is almost here, it's timely to consider that mutations that inactivate nucleotide-excision repair (NER) have been associated with several genetic diseases, such as xeroderma pigmentosum (XP). In humans, NER is the sole repair pathway for cyclobutane pyrimidine dimers, and thus people with XP are highly sensitive to light and are predisposed to sunlight-induced skin cancers.
A) In many microorganisms there is another pathway for repairing pyrimidine dimers. What is it?
B) A consequence of the inability to repair UV-induced photodimers is stalled replication forks. What are the two ways to repair (or bypass) stalled/collapsed replication forks that were mentioned in class?
C) In type G XP (XPG) cells replicate normally in the absence of UV-induced DNA damage. Which step in the NER pathway is presumably defective in XPG patients?
D) In a laboratory experiment cultures of fibroblasts from healthy individuals and from XPG patients are irradiated with UV light. The DNA is isolated and denatured, and it is found that the samples from the normal patients show a significant reduction in the average molecular weight of ssDNA after UV exposure, but the XPG fibroblasts do not show the same reduction. Explain this observation.