Question

Xeroderma pimentosum is a genetic disease involving mutations in any one of eight different genes encoding proteins/enzymes involved in UV-induced DNA damage repair.

a. How does UV produce mutations in DNA?

b. As knocking out 8 genes at the same time is close to impossible to accomplish in the lab, how were these 8 individual genes identified?

Answer 1

UV light produces mutations in DNA:

UV light is a potential mutagen that gives rise to Thymidine Dimer or 6-4 photoproducts which are produced by linking of thymidine of the same strand.These dimers are not replicated using the DNA polymerase III and thus Error prone polymerase replicate these strands with wrong bases opposite to these mutations,thereby giving rise to mutations.

b.The 8 individual genes were identified using genetic complementation test.

In this test the fusion of cells from different patients having different defects were fused to see if these cells complement each other, if complementation occurs then different genes were defective in each other.

So complementation groups were created by fusing somatic cells via somatic cell hybridization to see if different XP patients created complementation or not.Those that complemented did not have the same defective gene.by this method seven complementation groups were identified inferring seven factors that take part in repair of Uv damage and defect in anyone can give rise to Xeroderma Pigmentosum