Xeroderma pigmentosum (XP) is an autosomal recessive condition characterized by moderate to severe sensitivity to ultraviolet (UV) light. Patients develop multiple skin lesions on UV-exposed skin, and skin cancers often develop as a result. XP is caused by deficient repair of DNA damage from UV exposure.

A series of 10 skin-cell lines was grown from different XP patients. Cells from these lines were fused, and the heterokaryons were tested for genetic complementation by assaying their ability to repair DNA damage caused by a moderate amount of UV exposure. In the table below, '+' indicates that the fusion cell line performs normal DNA damage mutation repair, and '−' indicates defective DNA repair. Use this information to determine how many DNA-repair genes are mutated in the 10 cell lines, and identify which cell lines share the same mutated genes. 

Key Concepts

Xeroderma Pigmentosum (XP)

Xeroderma pigmentosum is a genetic disorder caused by mutations in genes responsible for repairing DNA damage induced by ultraviolet (UV) light. It is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene to exhibit symptoms. Patients with XP are highly sensitive to UV light, leading to skin lesions and an increased risk of skin cancers due to the accumulation of unrepaired DNA damage.

Genetic Complementation

Genetic complementation is a method used to determine whether two mutations that produce a similar phenotype are in the same gene or in different genes. In the context of XP, when cell lines from different patients are fused, the resulting heterokaryons can be tested for their ability to repair DNA damage. If the fused cells can repair DNA, it suggests that the mutations are in different genes, while failure to repair indicates that both mutations affect the same gene.

DNA Repair Mechanisms

DNA repair mechanisms are cellular processes that correct damage to the DNA molecule, ensuring genomic stability. In XP, the nucleotide excision repair (NER) pathway is primarily affected, which is responsible for removing UV-induced DNA lesions. Understanding these mechanisms is crucial for analyzing the results of the complementation tests, as it helps identify which specific genes are mutated in the cell lines and how they contribute to the overall DNA repair capacity.