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.

How does UV produce mutations in DNA?

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

Solution: Xeroderma pigmentosum(XP) is an autosomal recessive disease. The child having Xeroderma pigmentosum mutation is likely to develop skin cancer on regions of body exposed to sunlight. In normal man the mutation due to UV can be repaired by specificrepair pathways but in XP cells the mutation results in the failure to incorporate thymidine after exposure to UV. Also the nuclotide excision repair syatem active in normal individuals were missing in XP cells.

Several invitro assays were developed for the detection of different XP proteins. The Isolation of XP proteins was greatly facilitated by the availability of XP cell lines with specific XP protein defects. Cell-free extracts from normal cells were subjectd to standard protein fractionation techniques and analysed whether they could complement the activity of an  extract prepared from an XP cell line with a known defect.